Summary
This systematic review examined whether LDL cholesterol (LDL-C) is associated with mortality in people aged 60 and older, an age group in which the predictive value of cholesterol is increasingly uncertain. The authors identified 19 studies comprising 30 cohorts and a total of 68,094 older adults from the general population, tracking all-cause and cardiovascular mortality.
For all-cause mortality, data from 28 cohorts showed that 16 cohorts—representing 92% of participants—had an inverse association between LDL-C and mortality, meaning higher LDL-C was linked to lower death rates; in most of these, the association was statistically significant. The remaining cohorts showed no association, and none found that higher LDL-C increased mortality risk. For cardiovascular mortality, 2 of 9 cohorts reported significantly higher death rates in individuals with the lowest LDL-C, while the other 7 found no relationship.
Overall, the findings indicate that in adults over 60, higher LDL-C is not associated with increased risk of death and is often linked to greater longevity. This challenges the assumption that LDL-C is inherently harmful in older populations and suggests that aggressive LDL-lowering strategies in this age group may warrant re-evaluation, particularly for population-wide preventive approaches rather than individualized clinical care.
PMID: 27292972
PMCID: PMC4908872
DOI: 10.1136/bmjopen-2015-010401
Abstract
Objective: It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.
Setting, participants and outcome measures: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.
Results: We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.
Conclusions: High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.
Keywords: EPIDEMIOLOGY; GERIATRIC MEDICINE; PREVENTIVE MEDICINE; Risk factor, LDL-cholesterol, cardiovascular mortality, total mortality, elderly,.
Ravnskov U, Diamond DM, Hama R, Hamazaki T, Hammarskjöld B, Hynes N, Kendrick M, Langsjoen PH, Malhotra A, Mascitelli L, McCully KS, Ogushi Y, Okuyama H, Rosch PJ, Schersten T, Sultan S, Sundberg R. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open. 2016 Jun 12;6(6):e010401. doi: 10.1136/bmjopen-2015-010401. PMID: 27292972; PMCID: PMC4908872.