The cholesterol paradox in old age

In people in their late 80s and 90s, higher cholesterol often goes with lower death rates over the next few years, the opposite of the midlife pattern. The most likely explanation is that illness lowers cholesterol, though that is not fully settled. And cholesterol has not stopped mattering at that age: in healthy older people, high LDL cholesterol still goes with more heart attacks.

Don't read a high cholesterol in old age as protective. In a frail, very old person a low reading is often a sign of illness rather than its cause. Whether to start or stop treatment late in life is a separate question, covered in Lipid management.

What the paradox is

Two recent studies show the pattern, and both are small and based on a single cholesterol reading taken in old age.

Sardinia. Among 168 people aged 90 and over in the island's longevity hot spot, those with LDL cholesterol (LDL-C) of 3.4 mmol/L (130 mg/dL) or more lived about a year longer on average over six years of follow-up.^[1]
China. Among 903 adults aged 85 and over, total cholesterol of 3.4 mmol/L (131 mg/dL) or more went with about 30% lower death rates over three years, though in the study's own curves the link was not statistically clear at any single level.^[2]

Why illness is the usual explanation

The usual explanation is reverse causation. Serious illness, frailty, malnutrition and hidden cancer all lower cholesterol, so a low reading in the very old often marks decline rather than causing it. A single reading late in life cannot separate the two.

That reading is the mainstream one, not a consensus. The Sardinian authors argue the pattern is real rather than an artefact of illness.

Cholesterol still predicts heart disease in older people

Two large studies show that the link between cholesterol and heart disease does not disappear with age.

Across 61 cohorts of almost 900,000 adults free of heart disease at the start, each 1 mmol/L (39 mg/dL) lower total cholesterol still went with about a sixth fewer heart-disease deaths at ages 70–89.^[3]
In a Danish cohort of 91,131 adults aged 20–100 with no heart disease or diabetes and not on statins, higher LDL-C went with higher heart-attack risk at every age, and the number of extra heart attacks linked to it was highest at 70–100. Among those aged 80–100, LDL-C of 5 mmol/L (193 mg/dL) or more meant about three times the heart-attack risk of LDL-C below 3 mmol/L (116 mg/dL).^[4]

The genetic view: a lifetime, not one frail year

Genetic (Mendelian randomisation) studies use inherited differences in cholesterol, so they capture decades of exposure rather than one reading in old age. They point the same way as the midlife evidence.

Drawing on lifespan data for about a million people, genetically higher LDL-C (by one standard deviation) meant about 1.2 years shorter life.^[5]
In UK Biobank, people carrying genes for about 0.24 g/L higher apoB, the protein that marks each plaque-building particle, had parents who died roughly half a year to a year earlier, and about 2 years earlier once LDL-C and triglycerides were accounted for.^[6]

Low cholesterol in a 95-year-old can mean illness; low cumulative apoB across a lifetime means protected arteries. They are not the same measurement. The wider case is in Cholesterol.

The review that claimed it disproves the cholesterol story

A widely shared review has been used to argue that this pattern disproves the cholesterol story altogether. Of 28 cohorts of people over 60, it counted 16 where higher LDL-C went with lower overall mortality and found no link in the rest.^[7]

An independent appraisal by Oxford's Centre for Evidence-Based Medicine found serious weaknesses: no predefined protocol, a search of a single database that excluded 263 of 282 screened articles without per-study reasons, no meta-analysis, and no control for confounding (for example, people with high LDL-C starting statins during follow-up), which it judged more likely to explain most of the inverse associations. About two-thirds of the participants also came from a single study.^[8] It cannot outweigh the genetic and trial evidence.

What to do

Don't take the paradox as licence to ignore a high apoB or LDL-C in midlife. It concerns single readings in the very old.
In healthy older adults, treat high LDL-C as a heart risk. The risk did not fade with age in the Danish data.
In a frail, very old person, read a low cholesterol as a possible sign of illness, and see Blue Zones for how to read longevity-population data without over-fitting.