Elsevier

The Lancet

Volume 358, Issue 9279, 4 August 2001, Pages 351-355
The Lancet

Articles
Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study

https://doi.org/10.1016/S0140-6736(01)05553-2Get rights and content

Summary

Background

A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality.

Methods

Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71–93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models.

Findings

Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68·3, 48·9, 41·1, and 43·3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0·72 (95% CI 0·60–0·87), 0·60 (0·49–0·74), and 0·65 (0·53–0·80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1·64, 95% CI 1·13–2·36).

Interpretation

We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4·65 mmol/L) in elderly people.

Introduction

High concentration of total serum cholesterol is known to be directly related to mortality in individuals aged younger than 65 years. Previous clinical trials have not had large numbers of patients aged older than 70 years, and researchers have been unable to conclusively show this relation in elderly people.1, 2 Results of several studies have shown an inverse relation, or no relation, between total cholesterol concentration and risk of death in elderly people.3, 4, 5, 6 A U-shaped distribution has also been recorded, in which low concentrations of serum cholesterol in elderly people predict increased mortality.7 These findings suggest that cholesterol metabolism and homoeostatic mechanisms might differ between older and younger populations.

Corti and colleagues8 however, suggested that frailty (or disease) in elderly people is more likely to contribute to decreased survival than low cholesterol alone. They took data from the Established Populations for Epidemiologic Studies in the Elderly, in which 4066 patients had serum lipids measured and were followed up for 4 years, and adjusted the analysis for frailty measures (concentrations of albumin and iron in serum). The modified analysis showed that the relation between total cholesterol and coronary heart disease mortality in elderly people was the same as it was for younger and middleaged individuals. The researchers therefore concluded that the usual statistical adjustments for traditional coronary heart disease risk factors (ie, excluding older persons from cholesterol screening) do not account for possible changes associated with frailty, and are therefore inappropriate.8

By contrast, Manolio and colleagues9 pooled data from several studies and showed that total cholesterol concentration was significantly correlated with fatal coronary heart disease in both men and women across a broad age range and well into older populations (ages 65–100 years). The relative risk of mortality nonetheless lessened with increasing age. Such reductions in risk of mortality in elderly people could be because elderly people generally have a higher attributable risk.10 Clearly, whether the total concentration of cholesterol in serum has the same relation to mortality in older people as it does in younger people is not conclusive. These differing opinions have direct clinical relevance, since a judgment about total cholesterol and mortality in the elderly agegroup should precede screening and attempts to lower serum cholesterol concentrations.

We have therefore assessed changes in various lipid concentrations over about 20 years from 1972 to 1992 and correlated them with all-cause mortality in a large cohort of Japanese/American men who were followed up in the Honolulu Heart Program. Such longitudinal data for serum cholesterol concentration are not available from cross-sectional studies or from shorter follow-up times.

Section snippets

Study population

The Honolulu Heart Program is a longitudinal epidemiological study of cardiovascular disease which began with 8006 Japanese/American men, living on the island of Oahu, Hawaii in 1965. The men were born between 1900 and 1919 (age 45–68 years at the time of the first examination in 1965–68). Details of the selection process for the cohort have been published.11 The entire cohort has undergone six examinations so far. This report is based on the fourth examination of the cohort which was done in

Results

Mean cholesterol concentration fell significantly with increasing age—from 5·00 mmol/L in those aged 71–74, to 4·93 mmol/L in those aged 75–79, to 4·85 mmol/L in those aged 80–84, and 4·61 mmol/L in those aged older than 85 years (test for trend p<0·0001) (figure 1). Mortality rates were significantly higher in the 20% nonrespondents than in those who participated in the fourth examination. The rates for non-respondents were high even when compared with those in the lowest quartile of

Discussion

Our data accord with previous findings of increased mortality in elderly people with low serum cholesterol, and show that long-term persistence of low cholesterol concentration actually increases risk of death. Thus, the earlier that patients start to have lower cholesterol concentrations, the greater the risk of death. Cholesterol metabolism and homoeostatic mechanisms might differ in the very old (>75 years), and little information is available about cholesterol-mortality relations in this

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