Total cholesterol and risk of mortality in the oldest old

doi:10.1016/S0140-6736(97)04430-9

The Lancet

Volume 350, Issue 9085, 18 October 1997, Pages 1119-1123

https://doi.org/10.1016/S0140-6736(97)04430-9 Get rights and content

Summary

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, 5·0–6·4 mmol/L, and ⩾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% Cl 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.

Introduction

The importance of hypercholesterolaemia as a risk factor for cardiovascular disease in middle-aged people suggests that cholesterol-lowering therapy should be used to prevent morbidity and mortality. Above age 70 years, the significance of hypercholesterolaemia as a cardiovascular risk factor is controversial. The results of observational studies are conflicting, and data from controlled clinical trials on the effect of cholesterol lowering in the elderly are rare. Even if mechanisms of cardiovascular disease are the same for middle-aged and older people, the greater comorbidity and poorer health status in the elderly—as well as the cumulative years of risk exposure—hamper the generalisation of epidemiological results from younger to older individuals. Whether or not hypercholesterolaemia in elderly people with cardiovascular disease should be treated is therefore contested.

The finding that low cholesterol concentrations may be associated with increased mortality risk from cancer, respiratory disease, and trauma,¹ had also caused discussion. Some outcomes of clinical-intervention trials with cholesterol-lowering drugs suggest a similar increased mortality risk among the members of the actively treated group.2, 3 To explore further the relation between cholesterol as a risk factor for cardiovascular disease in the elderly, we assessed the effects of total cholesterol concentrations on specific and all-cause mortality in the Leiden 85-plus study.

Section snippets

Leiden 85-plus study

On Dec 1, 1986, the community of Leiden in the Netherlands had 105 000 inhabitants, of whom 1258 (1·2%) were 85 years and older. Among these oldest old, we initiated a population-based prospective follow-up study to assess the association of HLA antigens with human lifespan.4, 5 During the assessment, which lasted from Dec 1, 1986, to March 1, 1988, 221 participants died before they could be visited. A total of 1037 people were eligible for the study, of whom 977 (94%) provided informed consent

Zutphen study

To obtain information on total cholesterol distribution from a comparable birth cohort at a younger age (born 1900–10), we used data on total cholesterol from the Zutphen Study—a longitudinal, population-based study of risk factors for chronic diseases among middle-aged men in the town of Zutphen in the Netherlands.9, 10 In 1960, a random sample of 1088 men was drawn from a total population of 2450 men, born 1900–19. 878 men aged 40–59 years were examined, and their serum samples stored at

Statistical analysis

Data are presented as mean (SD) unless otherwise stated. We compared groups by means of the Student's t test. Survival was estimated with the Kaplan-Meier product-limit method, compared with the log-rank test, and stratified for age and sex. Survival time for participants was defined as the period from the date of the home visit to the date of one of the following events: death from a specific cause, death from any cause, and Oct 1, 1996. Mortality risks and 95% CIs for the three categories of

Results

724 participants aged 85 years and older for whom total cholesterol concentrations were available are included in this analysis. Their baseline characteristics (table 1) did not differ from those of participants whose total cholesterol concentrations were unavailable (data not shown). The 724 participants are from a cohort of 1037 people in an impact study of the HLA system and survival (Leiden 85-plus study). Compared with the 1037 people eligible for the study, the cumulative 10-year

Discussion

The results of our study show that for both men and women of 85 years and older, high total serum cholesterol concentrations are inversely correlated with mortality—ie, high cholesterol is associated with increased survival. Compared with participants who had low total cholesterol concentrations, those with moderately high and high concentrations have a lower mortality risk of of 22% and 38%, respectively.

The total cholesterol concentration of the participants aged 85 years and over might not

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Preoperative malnutrition as assessed by objective nutritional scores was associated with 1-year mortality after valvular heart surgery. The Controlling Nutritional Status score had the highest predictive ability and, when added to the European System for Cardiac Operative Risk Evaluation II, provided more accurate risk stratification.
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Cardiovascular risk in the elderly population of Spain. The EPICARDIAN risk score
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La estimación del riesgo cardiovascular en personas mayores de 70 años es problemática. La mayoría de las escalas se han creado basándose en cohortes de personas de mediana edad, con una representación insuficiente de los adultos de más edad. El poder predictivo de los factores de riesgo cardiovascular clásicos disminuye con la edad. El objetivo de este estudio es desarrollar una escala específica para estimar el riesgo cardiovascular de la población anciana española.
Este estudio se realizó en una cohorte poblacional establecida en 1995. Marco: 3 zonas geográficas de España (Madrid, Ávila y Lugo). Participantes: 3.729 personas mayores de 64 años sin enfermedades cardiovasculares (ECV) al inicio del seguimiento. Mediciones: se investigaron anualmente las sospechas de ECV mortal y no mortal (cardiopatía coronaria e ictus) y se confirmaron usando los criterios del proyecto MONICA de la OMS. Se siguió a todos los participantes hasta que apareció el primer episodio de ECV, hasta su muerte o hasta el 31 de diciembre de 2015.
La edad fue el factor predictivo más potente de ECV a los 10 años en ambos sexos. Las variables asociadas con ECV en los varones fueron el tratamiento de la hipertensión arterial (HR: 1,35; IC 95%: 1,067-1,710), la diabetes (HR: 1,359; IC 95%: 0,997-1,852) y el tabaquismo (HR: 1,207; IC 95%: 0,945-1,541), y en las mujeres, el tabaquismo (HR: 1,881; IC 95%: 1,356-2,609) y la diabetes (HR: 1,285; IC 95%: 0,967-1,707). El colesterol total no aumentó el riesgo de ECV ni en varones ni en mujeres. Sin embargo, las concentraciones de colesterol total > 200 mg/dL se asociaron inversamente al riesgo de ECV a los 10 años, tanto en varones como en mujeres.
La ECV total a los 10 años aumenta significativamente en los varones españoles de edad avanzada con la edad, la diabetes y el tratamiento antihipertensivo, y en las mujeres con la diabetes y el tabaquismo. Los niveles de colesterol total no aumentaron el riesgo de ECV, sobre todo en los varones.
Cardiovascular risk estimation in people over 70 years of age is problematic. Most scores have been created based on cohorts of middle-aged people, with an underrepresentation of older adults. The predictive power of classical cardiovascular risk factors declines with age. The aim of this work is to develop a specific score for estimating cardiovascular risk among the elderly population in Spain.
This work is a population-based cohort established in 1995. Setting: 3 geographical areas of Spain (Madrid, Ávila, and Lugo). Participants: 3,729 people older than 64 years with no cardiovascular diseases (CVD) at baseline. Measurements: suspected fatal and nonfatal CVD (both coronary heart disease and stroke) were investigated annually and confirmed using the WHO-MONICA criteria. All participants were followed-up on until occurrence of a first CVD event, until death, or until December 31, 2015.
Age was the strongest predictor of CVD at 10 years in both men and women. In men, variables associated with CVD were high blood pressure treatment (HR: 1.35; 95% CI: 1.067-1.710), diabetes (HR: 1.359; 95% CI: 0.997-1.852), and smoking (HR: 1.207; 95% CI: 0.945-1.541) and in women, the variables were smoking (HR: 1.881; 95% CI: 1.356-2.609) and diabetes (HR: 1.285; 95% CI: 0.967-1.707). Total cholesterol did not increase the risk of CVD in men or women. However, total cholesterol levels > 200 mg/dL were inversely associated with 10-year risk of CVD in men and women.
In elderly Spanish men, total CVD at 10 years is significantly increased by age, diabetes, and antihypertensive treatment and in elderly Spanish women by diabetes and smoking. Total cholesterol levels did not increase the risk of CVD, particularly in males.
Value of total cholesterol readings earlier versus later in life to predict cardiovascular risk
2021, EBioMedicine
Prognostic implications of blood cholesterol may differ at different stages of life. This cohort study compares the value of total cholesterol (TC) readings earlier versus later in life for the prediction of coronary atherosclerosis, cardiovascular events, and cardiovascular death.
In a cardiovascular observation study (CVOS) we performed coronary angiography and prospectively recorded cardiovascular events in 1090 patients over up to 19 years. These patients had participated in a health survey (HS) 15 years prior to the CVOS baseline. TC was measured twice, first at the earlier HS and then later at CVOS recruiting.
Patients in the highest versus the lowest TC-category of the HS had an OR of 4.30 [2.41–7.65] for significant CAD at angiography, a HR of 1.74 [1.10–2.76] for cardiovascular events, and a HR of 7.55 [1.05–54.49] for cardiovascular death after multivariate adjustment. In contrast, TC as measured at the baseline of the CVOS was neither significantly associated with significant CAD (OR= 0.75 [0.49–1.13]) nor with cardiovascular events or death during follow-up (HR= 0.86 [0.62–1.18] and 0.79 [0.41–1.53], respectively). Moreover, the ESC/EAS-SCORE was found to be more powerful in predicting cardiovascular mortality when using earlier instead of later TC, with a continuous net reclassification improvement of 0.301 (p<0.001).
Early measurement not only enables early intervention in keeping with the concept of lifelong exposure to atherogenic lipoproteins. These data also suggest that cardiovascular risk prediction is more accurate if using earlier in life TC readings.
The present study did not receive any particular funding

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ArticlesTotal cholesterol and risk of mortality in the oldest old

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Leiden 85-plus study

Zutphen study

Statistical analysis

Results

Discussion

Arch Gerontol Geriatr

J Chron Dis

Report of the conference on low blood cholesterol: mortality associations

Circulation

Lowering cholesterol concentrations and mortality: a quantative review of primary prevention trials

BMJ

The effect of pravastin on coronary events after myocardial infarction in patients with average cholesterol levels

N Engl J Med

The association between human leucocyte antigens (HLA) and mortality in community residents aged 85 and over

J Am Geriatr Soc

Validation of medical history taking as part of a population based survey in subjects aged 85 and over

BMJ

International classification of diseases: manual of the international statistical classification of diseases, injuries, and causes of death

Trends in infectious diseases mortality in the United States

JAMA

Serum cholesterol and 25-year incidence of and mortality from infarction and cancer

Arch Intern Med

Repeated measurements of serum cholesterol and blood pressure in relation to long-term incidence of myocardial infarction

Cardiology

Geriatric clinical chemistry reference values

Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons

Ann Intern Med

Articles
Total cholesterol and risk of mortality in the oldest old