Canibais e Reis

Conversava eu com um senhor de 77 anos, por quem tenho uma enorme estima, sobre assuntos não relacionados com saúde. A certa altura, por uma razão qualquer, comentou estar com colesterol alto, e até me pareceu algo preocupado com isso. Tentei tranquiliza-lo, dizendo que colesterol em alta nos seniores é um marcador de longevidade e saúde, que colesterol em declínio é um marcador de proximidade da morte, que o nível de colesterol quase não tem associação com doença cardiovascular nos idosos, e que colesterol baixo está associado a maior risco de cancro, infecções, depressão e suicídio. E ainda acrescentei que, inclusivamente, idosos com colesterol alto, após um infarto do miocárdio ou um AVC, têm maior taxa de sobrevivência, e que baixar colesterol com medicamentos não lhes prolonga a vida, no máximo modifica o tipo de morte, de cardiovascular para cancerosa. Por acaso, ao nosso lado estava outro sénior, também na casa dos 70 anos, que prontamente contrapôs, com a sua certeza, que isso não podia ser, que eu estava certamente equivocado. Dado o contexto em que esta conversa se desenrolou, não seria elegante da minha parte entrar em contraditório, pelo que calei-me e não disse mais nada. Para quem possa estar interessado no assunto, nomeadamente pessoas idosas que estão a tomar estatinas para baixar o colesterol, esse "assassino" moderno da nossa sociedade, segue-se mais abaixo a minha argumentação, expressa em citações da literatura médica. Quem estiver em desacordo com estas evidências, porventura suspeitando que eu possa ter feito uma escolha selectiva de estudos, por forma a favorecer a minha tese, por favor tenha a gentileza de igualmente contrapor com as respectivas citações da Pubmed, as quais eu terei todo o gosto em também listar neste blogue.

Colesterol alto nos idosos, longevidade e saúde
Nota: pode fazer o download em pdf da lista de artigos abaixo aqui.

 

J Am Geriatr Soc. 2005 Feb;53(2):219-26.

Relationship between plasma lipids and all-cause mortality in nondemented elderly.

Schupf N, Costa R, Luchsinger J, Tang MX, Lee JH, Mayeux R.
G. H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Abstract

OBJECTIVES: To investigate the relationship between plasma lipids and risk of death from all causes in nondemented elderly.

DESIGN: Prospective cohort study.

SETTING: Community-based sample of Medicare recipients, aged 65 years and older, residing in northern Manhattan.

PARTICIPANTS: Two thousand two hundred seventy-seven nondemented elderly, aged 65 to 98; 672 (29.5%) white/non-Hispanic, 699 (30.7%) black/non-Hispanic, 876 (38.5%) Hispanic, and 30 (1.3%) other.

MEASUREMENTS: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C, body mass index, and apolipoprotein E (APOE) genotype. clinical measures: neuropsychological, neurological, medical, and functional assessments; medical history of diabetes mellitus, heart disease, hypertension, stroke, and treatment with lipid-lowering drugs. Vital status measure: National Death Index date of death. Survival methods were used to examine the relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly, adjusting for potential confounders.

RESULTS: Nondemented elderly with levels of total cholesterol, non-HDL-C, and LDL-C in the lowest quartile were approximately twice as likely to die as those in the highest quartile (rate ratio (RR)=1.8, 95% confidence interval (CI)=1.3-2.4). These results did not vary when analyses were adjusted for body mass index, APOE genotype, diabetes mellitus, heart disease, hypertension, stroke, diagnosis of cancer, current smoking status, or demographic variables. The association between lipid levels and risk of death was attenuated when subjects with less than 1 year of follow-up were excluded (RR=1.4, 95% CI=1.0-2.1). The relationship between total cholesterol, non-HDL-C, HDL-C, and triglycerides and risk of death did not differ for older (>or=75) and younger participants (>75), whereas the relationship between LDL-C and risk of death was stronger in younger than older participants (RR=2.4, 95% CI=1.2-4.9 vs RR=1.6, 95% CI=1.02-2.6, respectively). Overall, women had higher mean lipid levels than men and lower mortality risk, but the risk of death was comparable for men and women with comparable low lipid levels.

CONCLUSION: Low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. More research is needed to understand these associations.

 

Lancet. 1997 Oct 18;350(9085):1119-23.

Total cholesterol and risk of mortality in the oldest old. (pdf)

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

Erratum in: Lancet 1998 Jan 3;351(9095):70. Comment in: ACP J Club. 1998 May-Jun;128(3):76.

Abstract

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: or = 6.5 mmol/L. 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 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.

 

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

Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality.

Ulmer H, Kelleher C, Diem G, Concin H.
Institute of Biostatistics and Documentation, Leopold Franzens University of Innsbruck, Innsbruck, Austria.

Abstract

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.

 

J Am Geriatr Soc. 2003 Jul;51(7):991-6.

Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging.

Brescianini S, Maggi S, Farchi G, Mariotti S, Di Carlo A, Baldereschi M, Inzitari D; ILSA Group.
Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Rome, Italy.

Abstract

OBJECTIVES: To analyze the relationship between serum total cholesterol (TC) and all-cause mortality, taking into account various potential confounders.

DESIGN: Population-based prospective cohort study.

SETTING: Older Italians residing in the general community.

PARTICIPANTS: Four thousand five hundred twenty-one men and women aged 65-84.

MEASUREMENTS: Vital status data were available for 1992-95. The hazard ratios of dying for subjects in the second, third, and fourth quartiles compared with the first quartile of TC were computed using Cox proportional hazards, adjusting for lifestyle factors, anthropomorphic and biochemical measures, preexisting medical conditions, and frailty indicators.

RESULTS: Blood samples were obtained from 3,295 (73%) of the participants, of whom 399 died during almost 3 years of follow-up. Low TC was associated with a higher risk of death. Those with TC in the second, third, and fourth quartiles (TC>189 mg/dL or 4.90 mmol/L) had lower hazard ratios (HRs) of death than subjects in the first quartile (0.57, 95% confidence interval (CI) = 0.38-0.87; 0.56, 95% CI = 0.36-0.88; and 0.53, 95% CI = 0.33-0.84, respectively). Few subjects taking lipid-lowering drugs (LLDs) were in the lowest quartile of cholesterol, suggesting that these individuals have low TC values for reasons other than LLD use.

CONCLUSION: Subjects with low TC levels (

 

Eur J Intern Med. 2009 Mar;20(2):139-44. Epub 2008 Jul 26.

Hypercholesterolaemia and risk of coronary heart disease in the elderly: impact of age: the Copenhagen City Heart Study.

Iversen A, Jensen JS, Scharling H, Schnohr P.
The Copenhagen City Heart Study, Bispebjerg University Hospital, Denmark.

Abstract

BACKGROUND: Population and interventional studies have shown that high plasma-cholesterol is a risk factor of coronary heart disease (CHD). However, in most of the studies elderly people were excluded.

AIM: This paper assesses whether the effect of total plasma-cholesterol on the risk of incident CHD decreases with age in a healthy population.

METHODS: Within the Copenhagen City Heart Study in 1981-1983, 4647 men and 5829 women, aged 40-93 years, underwent a cardiovascular health examination including measurement of plasma-cholesterol. The cohort was followed with respect to incident CHD until 1994, i.e. before statins were introduced in Denmark.

RESULTS: In people below 60 years of age plasma-cholesterol levels on 5-6; 6-8; and >8 mmol/L were associated with relative risks of CHD on 2.0 (95% confidence interval (CI) 1.2-3.2, P=0.004); 3.1 (CI 2.0-5.0, P8 mmol/L was associated with relative risks on 1.3 (CI 1.0-1.8, P=0.03), and 2.3 (CI 1.6-3.4, P8 mmol/L conferred increased relative risk on 1.6 (CI 1.2-2.4, P=0.007). In people above 80 years of age increased plasma-cholesterol was not associated with increased risk of incident CHD.

CONCLUSION: The risk of incident CHD associated with high plasma-cholesterol declines with age. This finding should be considered in future recommendations of plasma-cholesterol levels in elderly people without atherosclerotic cardiovascular disease.

 

J Hypertens. 1990 Aug;8(8):755-61.

Is a high serum cholesterol level associated with longer survival in elderly hypertensives?

Staessen J, Amery A, Birkenhäger W, Bulpitt C, Clement D, de Leeuw P, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, et al.
Klinisch Laboratorium Hypertensie, Inwendige Geneeskunde-Cardiologie, U.Z. Gasthuisberg, Leuven, Belgium.

Abstract

The relationship between serum total cholesterol, measured at randomization, and mortality was investigated in 822 patients, who were followed for an average of 3.1 years in a double-blind trial, conducted by the European Working Party on High Blood Pressure in the Elderly. Serum cholesterol, measured at randomization, was 0.54 mmol/l higher in women than in men, and declined with increasing age in both men (0.028 mmol/l per year) and women (0.036 mmol/l per year). During follow-up on randomized treatment, cholesterol fell by a similar amount with placebo (0.11 mmol/l per year) and with active treatment (0.14 mmol/l per year). Active treatment consisted of hydrochlorothiazide (25-50 mg/day) plus triamterene (50-100 mg/day) with the addition of alpha-methyldopa (0.5-2.0 g/day) in one-third of the patients. Serum total cholesterol, measured at randomization, was independently and inversely correlated with total (P = 0.03), non-cardiovascular (P = 0.03) and cancer (P = 0.04) mortality during follow-up on double-blind treatment. Total and non-cardiovascular mortality were also negatively correlated with haemoglobin and body weight at randomization.

 

Age Ageing. 2010 Nov;39(6):674-80. Epub 2010 Oct 14.

Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds.

Petersen LK, Christensen K, Kragstrup J.
Research Unit of Epidemiology, Danish Aging Research Center, University of Southern Denmark, Odense, Denmark.

Abstract

People aged 80 or older are the fastest growing population in high-income countries. One of the most common causes of death among the elderly is the cardiovascular disease (CVD). Lipid-lowering treatment is common, e.g. one-third of 75-84-year-old Swedes are treated with statins. The assumption that hypercholesterolaemia is a risk factor at the highest ages seems to be based on extrapolation from younger adults. A review of observational studies shows a trend where all-cause mortality was highest when total cholesterol (TC) was lowest (’a reverse J-shaped’ association between TC and all-cause mortality). Low TC (There is not sufficient data to recommend anything regarding initiation or continuation of lipid-lowering treatment for the population aged 80+, with known CVD, and it is even possible that statins may increase all-cause mortality in this group of elderly individuals without CVD.

 

J Hypertens. 2005 Oct;23(10):1803-8.

Role of modifiable risk factors in life expectancy in the elderly. (pdf)

Benetos A, Thomas F, Bean KE, Pannier B, Guize L.
Centre d’Investigations Préventives et Cliniques (IPC), Paris, and Department of Geriatrics, Medical School of Nancy, Nancy, France.

Abstract

OBJECTIVE: The aim of the present study was to evaluate the role of ‘modifiable’ risk factors, assessed between the ages of 60 and 70 years, in late survival.

DESIGN: The study population included subjects aged 60-70 years, who had a standard health examination at the IPC Center, and who could potentially reach the age of 80 years for men and 85 years for women at the end of the follow-up period.

METHODS: The role of ‘modifiable’ risk factors was assessed by comparing subjects who died before the age of 80 years for men (n=1333) and before 85 years for women (n=543) to subjects who survived beyond these ages (3681 men, 1910 women). Multivariate analyses were conducted to determine which parameters were independently associated with survival to an advanced age.

RESULTS: The multivariate analysis showed a decreased probability of late survival with higher pulse pressure (P

CONCLUSIONS: A systematic search for certain risk factors in an elderly patient can have a significant impact on late survival and can lead to the establishment of priority goals, such as increasing physical activity and reducing blood pressure, heart rate and glycemia.

 

J Am Geriatr Soc. 2005 Dec;53(12):2159-64.

Low-density lipoprotein cholesterol and mortality in older people.

Tikhonoff V, Casiglia E, Mazza A, Scarpa R, Thijs L, Pessina AC, Staessen JA.
Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.

Abstract

OBJECTIVES: To investigate the role of low-density lipoprotein cholesterol (LDL-C) as a predictor of mortality in elderly subjects.

DESIGN: Population-based prospective cohort study.

SETTING: Two communities in northern Italy.

PARTICIPANTS: Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years.

MEASUREMENTS: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL-C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity.

RESULTS: The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J-shaped), decreasing nonlinearly with LDL-C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL-C was J-shaped. The risk of fatal myocardial infarction was J-shaped in men, whereas it increased linearly with higher LDL-C in women. In both sexes, the association between stroke mortality and LDL-C was not significant.

CONCLUSION: This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people.

 

Age Ageing. 2008 Mar;37(2):207-13.

Relation of plasma lipids to all-cause mortality in Caucasian, African-American and Hispanic elders. (pdf)

Akerblom JL, Costa R, Luchsinger JA, Manly JJ, Tang MX, Lee JH, Mayeux R, Schupf N.
Department of Epidemiology, Columbia University, New York, USA.

Abstract

OBJECTIVES: to investigate the relation of plasma lipids to all-cause mortality in a multi-ethnic cohort of non-demented elderly.

SETTING: community-based sample of Medicare recipients, 65 years and older, residing in Northern Manhattan.

PARTICIPANTS: about two thousand five hundred and fifty-six non-demented elderly, 65-103 years. Among participants, 66.1% were women, 27.6% were White/non-Hispanic, 31.2% were African-American and 41.2% were Hispanic.

METHODS: a standardised assessment, including functional ability, medical history, physical and neurological examination and a neuropsychological battery was conducted. Vital status was ascertained through the National Death Index (NDI). We used survival analyses stratified by race and ethnicity to examine the relation of plasma lipids to subsequent all-cause mortality.

RESULTS: hispanics had the best overall survival, followed by African-Americans and Whites. Whites and African-Americans in the lowest quartiles of total cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol (LDL cholesterol) were approximately twice as likely to die as those in the highest quartile (White HR: 2.2, for lowest total cholesterol quartile; HR: 2.3, for lowest non-HDL cholesterol quartile; and HR: 1.8, for lowest LDL cholesterol quartile. African-American HR: 1.9, for lowest total cholesterol, HR: 2.0, for lowest non-HDL cholesterol and HR: 1.9, for lowest LDL cholesterol). In contrast, plasma lipid levels were not related to mortality risk among Hispanics.

CONCLUSIONS: hispanic ethnicity modifies the associations between lipid levels and all-cause mortality in the elderly.

 

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. (pdf)

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.

Comment in: JAMA. 1995 May 3;273(17):1330; author reply 1330-1.JAMA. 1995 May 3;273(17):1329; author reply 1330-1.JAMA. 1994 Nov 2;272(17):1372-4. JAMA. 1995 May 3;273(17):1329-30; author reply 1330-1.

Abstract

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 (

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 (

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.

 

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.

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 (

 

Gerontol A Biol Sci Med Sci. 2006 Jul;61(7):736-42.

Total serum cholesterol and recovery from disability among hospitalized older adults.

Onder G, Volpato S, Liperoti R, D’Arco C, Maraldi C, Fellin R, Bernabei R, Landi F; GIFA Investigators.
Department of Geriatrics, Catholic University of the Sacred Heart, Rome, Italy.

Abstract

BACKGROUND: The association between total serum cholesterol and health outcomes among older adults is controversial. The objective of the present study was to determine within a cohort of acutely hospitalized disabled elderly patients whether total cholesterol predicts recovery from disability in basic activities of daily living (ADL).

METHODS: Patients (3150) 65 years old or older admitted to 81 acute care units in Italy and presenting with ADL disability at hospital admission were included in this study. ADL disability was defined as need of assistance or total dependence in one or more ADLs (eating, dressing, personal hygiene, transferring, and toilet use). Recovery was defined as no disability at hospital discharge in any of the five ADLs considered.

RESULTS: Mean age of study participants was 80.5 +/- 7.2 years, and 1305 (41.1%) were men. The rate of recovery from ADL disability was 14.5% for participants with total cholesterol or = 240 mg/dL (n = 76/329). After adjustment for potential confounders, relative to that of patients with cholesterol or = 240 mg/dL. After exclusion of 769 patients with total cholesterol or = 240 mg/dL.

CONCLUSIONS: Among hospitalized disabled older adults, elevated levels of cholesterol are associated with increased rate of recovery from ADL disability.

 

Ann Epidemiol. 2004 May;14(5):325-31.

Predictors of falling cholesterol levels in older adults: the Cardiovascular Health Study.

Manolio TA, Cushman M, Gottdiener JS, Dobs A, Kuller LH, Kronmal RA; CHS Collaborative Research Group.
Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD 20892-7934, USA.

Abstract

PURPOSE: To estimate 4-year change in serum total cholesterol levels in a population-based sample of older adults and identify independent predictors of cholesterol decline.

METHODS: Prospective study of 2837 adults aged 65 years and older with serum cholesterol measured in 1992-1993 and 1996-1997.

RESULTS: Mean serum cholesterol levels declined 6.3 mg/dl between the two examinations. Declines were greater in white (-7.3 mg/dl) than black (-1.4 mg/dl) participants and in those in good/excellent health (-0.9 mg/dl) vs. fair/poor health (-3.1 mg/dl; both p

CONCLUSION: Declining cholesterol levels were associated with male gender, advanced age, weight loss, and white blood cell count but not with C-reactive protein levels. The role of declining cholesterol synthesis, due to as yet undefined age-related changes or to cytokine-mediated reductions related to illness, should be examined to help clarify the mechanisms of the sometimes marked declines in cholesterol levels observed at advanced ages.

 

J Am Geriatr Soc. 2003 Jan;51(1):80-4.

Does inflammation or undernutrition explain the low cholesterol-mortality association in high-functioning older persons? MacArthur studies of successful aging.

Hu P, Seeman TE, Harris TB, Reuben DB.
Multicampus Program in Geriatric Medicine and Gerontology, UCLA School of Medicine, Los Angeles, California 90095, USA.

Abstract

OBJECTIVES: To explore the effect of inflammation and undernutrition on the association between hypocholesterolemia and higher overall mortality in high-functioning older persons.

DESIGN: Prospective cohort study.

SETTING: Three U.S. communities.

PARTICIPANTS: A cohort of 870 participants from the MacArthur Studies of Successful Aging.

MEASUREMENTS: Baseline information was obtained for serum levels of cholesterol, C-reactive protein, interleukin-6, and albumin; body mass index; prevalent medical conditions; health behaviors; and medications. Crude and multivariate logistic regression analyses were used to examine the association between serum total cholesterol levels and 7-year all-cause mortality, while adjusting for potential confounders.

RESULTS: In univariate analysis, the risk ratio of low serum total cholesterol level ( Sex was an important confounding variable that contributed to the observed inverse association between low serum cholesterol and overall mortality in univariate analysis.

CONCLUSIONS: Hypocholesterolemia is not an independent risk factor for increased overall mortality in high-functioning community-dwelling older men and women. The association between low total cholesterol and high mortality observed in crude analysis is mainly confounded by common cardiovascular risk factors, rather than underlying inflammation or undernutrition.

Comment in J Am Geriatr Soc. 2004 Mar;52(3):469-70; author reply 471.

 

Am J Clin Nutr. 1995 Sep;62(3):547-53.

Low cholesterol concentrations in free-living elderly subjects: relations with dietary intake and nutritional status. (pdf)

Goichot B, Schlienger JL, Grunenberger F, Pradignac A, Aby MA.
Service de Médecine Interne, CHU Hautepierre, Strasbourg, France.

Abstract

Hypocholesterolemia has been reported in epidemiologic studies to be associated with increased mortality from noncardiovascular causes. Low cholesterol concentrations have been reported in various pathologic conditions and in institutionalized elderly patients, and seem to be associated with poor outcome. The role of nutritional factors in the genesis of hypocholesterolemia was investigated in 380 free-living elderly subjects. Subjects in the lowest cholesterol quartile had lower free triidothyronine and prealbumin concentrations and a lower Folstein’s score (a minimental test) than did those in the other quartiles. They did not differ from the other subjects for energy or nutrient intakes. Only 12 subjects (9 men and 3 women) had cholesterol concentrations These results indicate that low cholesterol concentration is a nonspecific feature of poor health status that is independent of nutrient or energy intake. The role of nutrient factors as a determinant of cholesterol concentration appears marginal in free-living elderly subjects.

 

Am J Med. 2003 Sep;115(4):265-71.

Serum cholesterol levels and in-hospital mortality in the elderly.

Onder G, Landi F, Volpato S, Fellin R, Carbonin P, Gambassi G, Bernabei R.
Department of Geriatrics, Catholic University of the Sacred Heart, Rome, Italy.

Abstract

PURPOSE: Although total cholesterol levels among middle-aged persons correlate with long-term mortality from all causes, this association remains controversial in older persons. We explored whether total cholesterol levels were independently associated with in-hospital mortality among elderly patients.

METHODS: We analyzed data from a large collaborative observational study, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), which collected data on hospitalized patients. A total of 6984 patients aged 65 years or older who had been admitted to 81 participating medical centers during four survey periods (from 1993 to 1998) were enrolled. Patients were divided into four groups based on total cholesterol levels at hospital admission: or=240 mg/dL (n = 940).

RESULTS: Patients (mean [+/- SD] age, 78 +/- 7 years) were hospitalized for an average of 15 +/- 10 days. The mean total cholesterol level was 186 +/- 49 mg/dL. A total of 202 patients died during hospitalization. Mortality was inversely related to cholesterol levels (or=240 mg/dL: 1.7% [16/940]; P for linear trend Compared with patients who had cholesterol levels or=240 mg/dL. These estimates were similar after further adjustment for inflammatory markers and after excluding patients with liver disease.

CONCLUSIONS: Among older hospitalized adults, low serum cholesterol levels appear to be an independent predictor of short-term mortality.

 

Age Ageing. 1999 May;28(3):313-5.

Cholesterol and long-term mortality after acute myocardial infarction in elderly patients. (pdf)

Bo M, Fiandra U, Fonte G, Bobbio M, Fabris F.
Institute of Geriatric Medicine and Surgery, University Turin, Italy.

Abstract

METHOD: We investigated the association of total serum cholesterol concentrations and subsequent overall and coronary mortality in 304 patients aged > or =65 discharged from hospital after acute myocardial infarction. RESULTS: There was no association between total cholesterol concentrations and mortality due to either coronary heart disease or to all causes in all patients or, separately, in men, women, patients younger than 75 and patients aged 75 years and older.

 

Exp Aging Res. 1998 Apr-Jun;24(2):169-79.

Serum cholesterol levels as a measure of frailty in elderly patients.

Ranieri P, Rozzini R, Franzoni S, Barbisoni P, Trabucchi M.

Abstract

The authors evaluated the association between serum cholesterol levels and social, clinical, and functional characteristics in 637 elderly hospitalized patients (mean age = 79.1 years, range = 65-97) from the Geriatric Evaluation and Rehabilitation Unit (GERU) at P. Richiedei Hospital in Gussago, Brescia (Italy). Patients consecutively admitted to the GERU during an 18-month period underwent a multidimensional evaluation including information on demographics, cognitive status, physical health (number of chronic diseases and administered drugs), functional disability, and nutritional status. Mean cholesterol levels were significantly lower in men; persons living with others; older individuals; and individuals with cognitive impairment, poorer somatic health, higher disability, and a higher level of malnutrition. Lower serum cholesterol levels may be considered an independent hematologic marker of frailty in elderly hospitalized patients.

 

Clin Chim Acta. 2000 Jan 5;290(2):213-20.

The possible association of decreased total cholesterol and severity of disease in elderly hospitalized patients.

Petersen JR, Linde MK, Bissell MG.
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0551, USA.

Abstract

The object of our study was to determine if any association exists between low serum cholesterol ( 60 years. Patients with low serum cholesterol were compared to a patient population with high serum cholesterol (> 6.22 mmol/l) and normal cholesterol (> or = 4.14 to Only hospitalized patients > 60 years, who were not on cholesterol lowering drugs, and did not have cardiovascular or liver disease were included in this study. The study group was 157 patients (79 with low, 78 with high, and 23 with normal cholesterol concentrations). Using the Kruskal-Wallis tests, the low cholesterol group was found to have statistically (p 11.1 days), higher hospital re-admission rate over a 1-year period (average difference of > 0.4 re-admissions), greater use of acute care services (average difference of > 0.6 days), and more emergency room (ER) visits over 1 year (average difference of > 0.5 admissions).

 

Scand J Prim Health Care. 2010 Jun;28(2):121-7.

Serum total cholesterol levels and all-cause mortality in a home-dwelling elderly population: a six-year follow-up. (pdf)

Tuikkala P, Hartikainen S, Korhonen MJ, Lavikainen P, Kettunen R, Sulkava R, Enlund H.
Department of Social Pharmacy, University of Kuopio and Kuopio Research Centre of Geriatric Care, Kuopio, Finland.

Abstract

OBJECTIVE: To investigate the association between serum total cholesterol and all-cause mortality in elderly individuals aged > or = 75 years. Design. A prospective cohort study with a six-year follow-up. SETTING AND SUBJECTS: A random sample (n = 700) of all persons aged > or = 75 years living in Kuopio, Finland. After exclusion of participants living in institutional care and participants using lipid-modifying agents or missing data on blood pressure and cholesterol levels, the final study population consisted of 490 home-dwelling elderly persons with clinical examination. We used the Cox proportional hazard model and the propensity score (PS) method. Main outcome measure. All-cause mortality. Results. In an age- and sex-adjusted analysis, participants with S-TC > or = 6mmol/l had the lowest risk of death (hazard ratio, HR = 0.48, 95% CI 0.33-0.70) compared with those with S-TC HR of death for a 1 mmol increase in S-TC was 0.78. In multivariate analyses, the HR of death for a 1 mmol increase in S-TC was 0.82 and using S-TC or = 6 mmol/l was 0.59 (95% CI 0.39-0.89) and for S-TC 5.0-5.9 mmol/l, the HR was 0.62 (95% CI 0.42-0.93). In a PS-adjusted model using S-TC or = 6 mmol/l was 0.42 (95% CI 0.28-0.62) and for S-TC 5.0-5.9 mmol/l, the HR was 0.57 (95% CI 0.38-0.84). Conclusions. Participants with low serum total cholesterol seem to have a lower survival rate than participants with an elevated cholesterol level, irrespective of concomitant diseases or health status.

 

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.

Abstract

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, 5.2 times higher than the minimum at serum cholesterol 4.0 mmol/l, and only 1.8 times higher when cholesterol concentration was 8.8 mmol/l. 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.

 

J Fam Pract. 2006 Apr;55(4):356-7.

Clinical inquiries. Should we identify and treat hyperlipidemia in the advanced elderly? (pdf)

Shah K, Rogers J, Britigan D, Levy C.
Department of Family and Community Medicine, Baylor College of Medicine, Houston, USA.

 

J Am Geriatr Soc. 2003 Jul;51(7):930-6.

Long-term prognostic importance of total cholesterol in elderly survivors of an acute myocardial infarction: the Cooperative Cardiovascular Pilot Project.

Foody JM, Wang Y, Kiefe CI, Ellerbeck EF, Gold J, Radford MJ, Krumholz HM.
Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.

Abstract

OBJECTIVES: To determine the long-term prognostic importance of in-hospital total serum cholesterol in elderly survivors of acute myocardial infarction (AMI).

DESIGN: Retrospective medical record review.

SETTING: Acute care, nongovernmental hospitals in Alabama, Connecticut, Iowa, and Wisconsin.

PARTICIPANTS: Four thousand nine hundred twenty-three Medicare beneficiaries from four states aged 65 and older discharged alive with a principal diagnosis of AMI between June 1, 1992, and February 28, 1993, who had a measurement of total serum cholesterol during hospitalization.

MEASUREMENTS: Primary endpoint of all-cause mortality within 6 years of discharge.

RESULTS: Of the 7,166 hospitalizations meeting study inclusion criteria, 4,923 (68.7%) had total cholesterol assessed, and 22% had a cholesterol level of 240 mg/dL or greater. Of AMI hospitalization survivors with cholesterol of 240 md/dL or greater, 17.2% died within 1 year and 47.9% died within 6 years, compared with 17.4% (P =.73) and 48.7% (P =.98) of those with a cholesterol level less than 240 mg/dL. The adjusted hazard ratio for elevated total serum cholesterol measured during hospitalization for all-cause mortality in the 6 years after discharge was 0.97 (95% confidence interval (CI) = 0.87-1.09). The unadjusted 1- and 6-year mortality rates for those with total cholesterol less than 160 mg/dL were 22.2% and 55.5%, respectively, not significantly different from mortality for patients with cholesterol of 160 mg/dL or greater, even after adjustment.

CONCLUSION: Among elderly survivors of AMI, elevated total serum cholesterol measured postinfarction is not associated with an increased risk of all-cause mortality in the 6 years after discharge. Furthermore, this study found no evidence of an increased risk of all-cause mortality in patients with low total cholesterol. Further studies are needed to determine the relationship of postinfarction lipid subfractions and mortality in older patients with coronary artery disease (CAD).

 

Eur Heart J. 1997 Jan;18(1):52-9.

Low total cholesterol is associated with high total mortality in patients with coronary heart disease. The Bezafibrate Infarction Prevention (BIP) Study Group. (pdf)

Behar S, Graff E, Reicher-Reiss H, Boyko V, Benderly M, Shotan A, Brunner D.
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel Hashomer, Israel.

Comment in: Eur Heart J. 1997 Aug;18(8):1357-9.Eur Heart J. 1997 Jan;18(1):6-9.

Abstract

The present non-intervention screening study was undertaken to explore the relationships between pre-existing low total cholesterol and all-cause mortality. Eleven thousand, five hundred and sixty-three patients with coronary heart disease who attended a screening visit but were not included in the Bezafibrate Infarction Prevention study were followed-up for a mean of 3.3 years after determination of baseline total cholesterol. Five hundred and ninety-five (5%) of this largely unselected population who had total cholesterol levels The most frequent cause of non-cardiac death associated with low total cholesterol was cancer. These results in patients with coronary heart disease add weight to previous studies associating low total cholesterol with an increased risk of non-cardiac death. However, a longer follow-up of this cohort of patients is necessary in order to clarify this association.

 

J Gerontol A Biol Sci Med Sci. 2004 Mar;59(3):293-7.

Low cholesterol levels are associated with short-term mortality in older patients with ischemic stroke.

Zuliani G, Cherubini A, Atti AR, Blè A, Vavalle C, Di Todaro F, Benedetti C, Volpato S, Marinescu MG, Senin U, Fellin R.
2nd Department of Internal Medicine, University of Ferrara, Italy.

Abstract

BACKGROUND: The possible relationship between serum total cholesterol (TC) levels and outcome following ischemic stroke is still controversial. We evaluated the association between TC levels and 30-day mortality in a sample of older patients with acute ischemic stroke.

METHODS: We enrolled 490 older patients with severe ischemic stroke consecutively admitted to University Hospital’s Internal Medicine or Geriatrics Department. Stroke type was classified according to the Oxfordshire Community Stroke Project. The data recorded included clinical features, medical history, electrocardiogram, and blood analyses. Patients were divided into three groups by TC levels: group I (TC5.2 mmol/L).

RESULTS: The overall mortality was 27.7%. Mortality was higher in patients with low TC levels (47.4%) compared with those with normal and high TC levels (23.0% and 24.1%, respectively). The odds ratio (OR) for short-term death was 2.17 (95% confidence interval [CI] 1.22-3.85) in group I compared with group III, after adjustment for age and gender. This result did not change after adjustment for possible confounders (OR 2.87; 95% CI 1.23-6.68). A similar trend was observed after adjustment for the Oxfordshire classification, age, and gender (OR 1.67; 95% CI 0.83-3.33).

CONCLUSIONS: Short-term mortality following ischemic stroke is higher in older participants with low TC levels, independent of a large number of factors. Low TC levels might be useful in identifying frail older participants at high risk of stroke short-term mortality.

 

IMAJ - VOL 13 - ma y 2011

Functional Outcome of Elderly Survivors of Ischemic Stroke: A Retrospective Study Comparing Non-Hypercholesterolemic and Hypercholesterolemic Patients (pdf)

Eliyahu Hayim Mizrahi MD MHA1,2, Anna Waitzman MD1, Marina Arad MD1,2 and Abraham Adunsky MD1,2
1Department of Geriatric Medicine and Rehabilitation, Sheba Medical Center, Tel Hashomer, Israel
2Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

Background: Total cholesterol is significantly associated with increased risk of ischemic stroke. Patients with ischemic stroke and high cholesterol levels may show better functional outcome after rehabilitation. Objectives: To study the possible interrelations between hypercholesterolemia and functional outcome in elderly survivors of ischemic stroke. Methods: We conducted a retrospective chart review study of consecutive patients (age ≥ 60 years) with acute stroke admitted to a geriatric rehabilitation ward in a university-affiliated hospital. The presence or absence of hypercholesterolemia was based on registry data positive for hypercholesterolemia, defined as total cholesterol ≥ 200 mg/dl (5.17 mmol/L). Functional outcome of patients with hypercholesterolemia (Hchol) and without (NHchol) was assessed by the Functional Independence Measurement scale (FIMTM) at admission and discharge. Data were analyzed by t-test and chi-square test,  as well as linear regression analysis. Results: The complete data for 551 patients (age range 60–96 years) were available for final analysis; 26.7% were diagnosed as having hypercholesterolemia. Admission total FIM scores were significantly higher in patients with Hchol (72.1 ± 24.8) compared with NHchol patients (62.2 ± 24.7) (P High cholesterol levels may be useful in identifying older individuals with a better rehabilitation potential.

 

Arterioscler Thromb Vasc Biol. 2004 May;24(5):962-8. Epub 2004 Mar 18.

Large artery stiffness is not related to plasma cholesterol in older subjects with hypertension. (pdf)

Dart AM, Gatzka CD, Cameron JD, Kingwell BA, Liang YL, Berry KL, Reid CM, Jennings GL.
Baker Heart Research Institute, LaTrobe University, Melbourne, Australia.

Abstract

OBJECTIVE: Previous studies have demonstrated a prognostic role of large artery stiffness in hypertensive subjects and increased stiffness in subjects with coronary artery disease. Although plasma cholesterol is an established risk factor for cardiovascular disease, its relationship with large artery properties in a hypertensive population is unclear.

METHODS AND RESULTS: Plasma cholesterol and large artery properties were measured at baseline in a subset of participants of a randomized controlled trial (ANBP2) evaluating hypertension treatment in older (65 to 84 years) subjects. Noninvasive measures of large artery behavior were central augmentation index (AI), systemic arterial compliance (SAC), and transverse expansion of the aortic arch (aortic distensibility). Arterial waveforms acceptable for analysis were obtained in approximately 80% of cases yielding valid measurements of AI in 868, SAC in 846, and aortic distensibility in 680 subjects. Mean total and high-density lipoprotein (HDL) concentrations were 5.5+/-1.0 and 1.4+/-0.5 mmol L(-1). Total and HDL cholesterol and AI were greater in females than males, whereas SAC and aortic distensibility were greater in males. In multiple regression analyses there were no significant associations between stiffness parameters and total or HDL cholesterol. Significant independent associations in such analyses were found for mean arterial blood pressure, gender, age, height, and heart rate, in keeping with previous findings.

CONCLUSIONS: In the largest cohort of elderly hypertensive subjects studied to date, plasma cholesterol per se was not associated with large artery stiffness. Such independence from cholesterol increases the potential for artery stiffness measurements to additionally contribute to cardiovascular risk assessment in this population.

 

J Biol Regul Homeost Agents. 2009 Jul-Sep;23(3):133-40.

The role of cholesterol levels in mood disorders and suicide.

De Berardis D, Conti CM, Serroni N, Moschetta FS, Carano A, Salerno RM, Cavuto M, Farina B, Alessandrini M, Janiri L, Pozzi G, Di Giannantonio M.

Abstract

The individuation of sensitive and specific biochemical markers, easily assessable on large samples of subjects and usefully employable as predictors of severe psychiatric disorders, such as mood disorders, could help clinicians to improve the diagnostic and therapeutic processes facilitating the long-term follow-up. In particular, serum cholesterol levels may potentially be optimal markers due to their relative easy sampling and low cost. The involvement of cholesterol in affective disorders such as Major Depression (MD), Seasonal Affective Disorder (SAD) and Bipolar Disorders (BD) is a debated issue in current research. However, current literature is controversial and, to date, it is still not possible to reach an agreement on its possible usefulness of cholesterol as a biological marker of affective disorders. Despite the controversial results on the relationships between cholesterol levels and affective disorders, the majority of literature seems to show a more consistent relationship between cholesterol levels and suicidal behaviour, with few studies that have found no relationships. The aim of this review is to elucidate current facts and views about the role of cholesterol levels in mood disorders as well as its involvement in suicidal behaviour.

 

J Psychosom Res. 1995 Jul;39(5):549-62.

Cholesterol and psychological well-being.

Wardle J.
Health Behaviour Unit, Institute of Psychiatry, University of London , UK.

Abstract

The debate about possible adverse effects associated with low or lowered serum cholesterol has raised important scientific questions concerning the links between lipids and behaviour. One of the most unexpected findings has been an association between cholesterol-lowering treatment and accidental death. A similar association has also emerged among the prospective cohort studies, with higher-than-expected numbers of suicide deaths in the lowest cholesterol groups. These observations have prompted speculation that behavioural or emotional disturbances could be part of the process linking lipids and accidental death. In this paper, the epidemiological literature is reviewed briefly, then the evidence for depression as a mediating condition is discussed. Two conclusions are drawn from this review of the literature. One is that understanding the relationship between the biology of lipids and the psychobiology of mood is demonstrably an important scientific and public health issue. The second is that the introduction of new treatments or preventive programmes should include a careful evaluation of the psychological as well as the physical effects.

 

Arch Cardiovasc Dis. 2010 Feb;103(2):61-5. Epub 2010 Feb 4.

Statins in the elderly: what evidence of their benefit in prevention? (pdf)

Steg PG, Tissot CM.

 

Assessment Program Volume 21, No. 12 February 2007 

Special Report: The Efficacy and Safety of Statins in the Elderly (pdf)

Technology Evaluation Center (Blue Cross and Blue Shield Association)

 

Lancet. 2002 Nov 23;360(9346):1623-30.

Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. (pdf)

Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk.
University Department of Pathological Biochemistry, University of Glasgow, Royal Infirmary, Scotland, Glasgow, UK.

Abstract

BACKGROUND: Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke.

METHODS: We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat.

FINDINGS: Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability.

INTERPRETATION: Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.

 

Arch Intern Med. 2010 Jun 28;170(12):1024-31.

Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. (pdf)

Ray KK, Seshasai SR, Erqou S, Sever P, Jukema JW, Ford I, Sattar N.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.

Comment in: Ann Intern Med. 2010 Sep 21;153(6):JC3-4.Arch Intern Med. 2010 Jun 28;170(12):1007-8.

Abstract

BACKGROUND: Statins have been shown to reduce the risk of all-cause mortality among individuals with clinical history of coronary heart disease. However, it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD.

DATA SOURCES: Trials were identified through computerized literature searches of MEDLINE and Cochrane databases (January 1970-May 2009) using terms related to statins, clinical trials, and cardiovascular end points and through bibliographies of retrieved studies.

STUDY SELECTION: Prospective, randomized controlled trials of statin therapy performed in individuals free from CVD at baseline and that reported details, or could supply data, on all-cause mortality.

DATA EXTRACTION: Relevant data including the number of patients randomized, mean duration of follow-up, and the number of incident deaths were obtained from the principal publication or by correspondence with the investigators.

DATA SYNTHESIS: Data were combined from 11 studies and effect estimates were pooled using a random-effects model meta-analysis, with heterogeneity assessed with the I(2) statistic. Data were available on 65,229 participants followed for approximately 244,000 person-years, during which 2793 deaths occurred. The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction (risk ratio, 0.91; 95% confidence interval, 0.83-1.01) in the risk of all-cause mortality. There was no statistical evidence of heterogeneity among studies (I(2) = 23%; 95% confidence interval, 0%-61% [P = .23]).

CONCLUSION: This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.

 

World Rev Nutr Diet. 2009;100:90-109. Epub 2009 Aug 17.

Cholesterol was healthy in the end. (pdf)

Ravnskov U.
Lund, Sweden.

 

World Rev Nutr Diet. 2009;100:80-9. Epub 2009 Aug 17.

Disappointing recent cholesterol-lowering drug trials: is it not time for a full reappraisal of the cholesterol theory? (pdf)

de Lorgeril M.

Coeur et Nutrition, Université Joseph Fourier-Grenoble 1, CNRS, Laboratoire TIMC-IMAG, UMR 5525, Faculté de Médecine, Grenoble, France.

 

Tidsskr Nor Laegeforen. 2004 Jan 22;124(2):167-9.

[Treatment with statins of the elderly].

[Article in Norwegian]

Holme I, Tonstad S.
Avdeling for epidemiologi og helseovervåkning, Klinikk for forebyggende medisin, Ullevål universitetssykehus, Oslo.

Abstract

BACKGROUND: Previous studies of treatment with statins have included few subjects aged 70 years or above. While the absolute risk of cardiovascular disease in the elderly is very high, the benefits of treatment may be reduced by adverse events, polypharmacy and competing risks.

MATERIAL AND METHODS: A statistician and a clinician reviewed the Pravastatin in elderly individuals at risk of vascular disease (PROSPER) study and compared the results with subgroup analyses of previous studies.

RESULTS: Subgroup analyses of previous studies showed that treatment with statins reduces cardiovascular events among patients with coronary heart disease aged > or = 65 years. The Heart Protection Study (HPS) included elderly with known atherosclerotic disease, while only 44% of subjects in the PROSPER study had such disease. Among subjects aged 70 or above the difference in events between the groups that received a statin or placebo was 6.1% in the HPS study and 2.1% in the PROSPER study (numbers needed to treat were 6 and 48, respectively). The studies gave conflicting results with regard to stroke and cancer.

INTERPRETATION: Elderly people with cardiovascular disease may benefit from treatment with statins. We do not have data that show that statins reduce total mortality among the elderly.

 

J Am Coll Cardiol. 2004 Sep 1;44(5):1009-10.

Low and lowered cholesterol and total mortality. (pdf)

Criqui MH, Golomb BA.

Comment on: J Am Coll Cardiol. 2004 Sep 1;44(5):1002-8.

 

Curr Opin Lipidol. 2001 Dec;12(6):601-9.

Issues surrounding age: vascular disease in the elderly. (pdf)

Shepherd J.
Institute of Biochemistry, Royal Infirmary, Glasgow, Scotland, UK.

Abstract

One-fifth of all humans who have survived beyond the age of 65 are alive today, and in the industrialized world the elderly segment of the population is expanding most rapidly. In biological terms, these survivors are healthier than the elderly of previous generations. However ‘there are no diseases peculiar to old age and very few from which it is exempt’ (Alfred Worcester, 1855-1951), and so society will inevitably accumulate a significant share of degenerative diseases within the ranks of its senior citizens. In the last two decades, the prevalence of stroke, diabetes mellitus, arthritis and heart disease has increased significantly as a tangible index of ageing in the population, and these diseases have been accompanied by degenerating cognitive function and physical disability, both of which are adding increasing stress to community healthcare and social services. Policy-makers need to understand and monitor these trends in order to make informed and cogent decisions about the management of this growing problem. This review highlights some of the key health issues facing the elderly in regard to coronary artery disease, insulin resistance, redox status, and statin therapy, in the hope that enlightened debate will inform decision making on resource allocation for this important and growing segment of society.

 

Geriatr Nephrol Urol. 1998;8(1):11-4.

The controversy surrounding cholesterol treatment in older people.

Alibhai SM, Rochon PA.

Abstract

The evidence of the benefit of lowering cholesterol levels in seniors from epidemiologic studies and RCTs is conflicting. Epidemiologic studies suggest that elevated cholesterol levels in elderly people may be a marker of good health. In some cases, lowering cholesterol in seniors may even prove harmful. Conversely, RCTs of lipid-lowering therapy have shown clear benefits in reducing coronary events in younger and middle-aged adults with or without pre-existing CAD. Both the epidemiologic studies and the RCTs we evaluated have methodologic concerns that make generalization to all seniors difficult. One epidemiologic study, in fact, found that there may be a physiologic decline in cholesterol levels as people age into their 70s and beyond [16]. We still do not appear to have a clear insight into the precise role cholesterol plays in seniors, especially those over the age of 75. In the future, as more data becomes available from RCTs and meta-analyses evaluating seniors in the older age group [15], we hope to have a better understanding of how to treat hypercholesterolaemia in this population. Until further studies are published, treatment plans need to be individualized, and the risks and benefits of treatment on various outcomes must be weighed according to the best evidence we have available.

 

Geriatric Times - May/June 2004 - Vol. V - Issue 3

Statin Adverse Effects: Implications for the Elderly

Beatrice A. Golomb, M.D., Ph.D.

 

Nutr Metab Cardiovasc Dis. 2007 Sep;17(7):e19-20; author reply e21-3. Epub 2007 Mar 27.

Statins for women, elderly: malpractice? (pdf)

Vos E.

Comment on Nutr Metab Cardiovasc Dis. 2006 Sep;16(6):391-4.

 

Statins and the Elderly (SpaceDoc)

Duane Graveline MD MPH.

 

Elder Care 2010

Hyperlipidemia in Older Adults: To Treat or Not to Treat? (pdf)

Carol L. Howe, MD, MLS, College of Medicine, University of Arizona. Barry D. Weiss, MD, College of Medicine, University of Arizona

 

QJM. 2001 Mar;94(3):127-32.

Age and gender bias in statin trials. (pdf)

Bandyopadhyay S, Bayer AJ, O’Mahony MS.
University Department of Geriatric Medicine, Llandough Hospital, Penarth, UK.

Abstract

Cardiovascular disease is strongly age-related, and is the leading cause of death in older people. Several well-publicized trials have recently reported that statin drugs (HMG CoA reductase inhibitors) are effective in lowering cholesterol and in reducing the risk of myocardial infarction and stroke. In order to determine whether the results of these trials are relevant to our ageing population, we examined the representation of older people and women in randomized controlled trials of statin drugs. A systematic search of the medical literature from 1990 to 1999 was done to identify randomized placebo-controlled trials of statin drugs which evaluated clinical end-points-myocardial infarction, stroke or death. We identified 19 trials: 15 secondary prevention and four primary prevention. The mean age, age range and gender of the participants in these trials were determined. In the secondary prevention trials, the total number of patients randomized was 31683, with a combined mean age of 58.1 years. No trial enrolled people beyond the age of 75 years, and only 23% of the trial population was female. The four primary prevention trials randomized a combined total of 14 557 subjects with a mean age of 56.9 years. Only 10% of study participants were female. Statin drug trials have suffered from age and gender bias, having been mainly conducted in middle-aged male populations. The extrapolation of evidence from these trials to older people and women needs further evaluation.

 

Curr Opin Cardiol. 2010 Jul;25(4):335-9.

Women and elderly: subgroups under-represented in clinical trials.

Devlin G.
University of Auckland Waikato Hospital, Hamilton, New Zealand.

Abstract

PURPOSE OF REVIEW: Women and older patients with cardiovascular disease are frequently underinvestigated and are less likely to receive evidence-based treatments than younger male counterparts. A lack of sex and age-specific clinical trial evidence is frequently cited for this practice. This manuscript reviews the currently available evidence base in the management of both groups presenting with ischaemic heart disease and heart failure.

RECENT FINDINGS: Registry data in both women and older patients confirm that these groups receive suboptimal care in the management of ischaemic heart disease and heart failure. A number of recent trials, including several meta-analyses, do not support this practice and suggest that, with the possible exception of implantable cardiac defibrillator implantation in females, both women and elderly patients derive similar benefit to younger males in the management of risk factors, symptomatic ischaemic heart disease and heart failure.

SUMMARY: Pending sex and age-specific trials to address in particular not only outcomes but dosing and complications, women and elderly patients should receive similar evidence-based treatment of cardiac risk factors, symptomatic ischaemic disease and heart failure to younger males.

 

BMJ. 2007 Aug 11;335(7614):285-7.

Preventive health care in elderly people needs rethinking. (pdf)

Mangin D, Sweeney K, Heath I.
Christchurch School of Medicine, University of Otago, Christchurch, New Zealand.

Comment in BMJ. 2007 Aug 25;335(7616):361-2.

 

BMJ 2009; 338:b873 doi: 10.1136/bmj.b873 (Published 3 March 2009)

Let’s not turn elderly people into patients (pdf)

Michael Oliver, professor emeritus of cardiology, University of Edinburgh.

Replies to Let’s not turn elderly people into patients