Monitoring cholesterol levels: measurement error or true change?

Cholesterol level monitoring is a common clinical activity, but the optimal monitoring interval is unknown and practice varies.

To estimate, in patients receiving cholesterol-lowering medication, the variation in initial response to treatment, the long-term drift from initial response, and the detectability of long-term changes in on-treatment cholesterol level ("signal") given short-term, within-person variation ("noise").

Analysis of cholesterol measurement data in the LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) study.

Randomized, placebo-controlled trial in Australia and New Zealand (June 1990 to May 1997).

9014 patients with past coronary heart disease who were randomly assigned to receive pravastatin or placebo.

Serial cholesterol concentrations at randomization, 6 months, and 12 months, and then annually to 5 years.

Both the placebo and pravastatin groups showed small increases in within-person variability over time. The estimated within-person SD increased from 0.40 mmol/L (15 mg/dL) (coefficient of variation, 7%) to 0.60 mmol/L (23 mg/dL) (coefficient of variation, 11%), but it took almost 4 years for the long-term variation to exceed the short-term variation. This slow increase in variation and the modest increase in mean cholesterol level, about 2% per year, suggest that most of the variation in the study is due to short-term biological and analytic variability. Our calculations suggest that, for patients with levels that are 0.5 mmol/L or more (> or =19 mg/dL) under target, monitoring is likely to detect many more false-positive results than true-positive results for at least the first 3 years after treatment has commenced.

Patients may respond differently to agents other than pravastatin. Future values for nonadherent patients were imputed.

The signal-noise ratio in cholesterol level monitoring is weak. The signal of a small increase in cholesterol level is difficult to detect against the background of a short-term variability of 7%. In annual rechecks in adherent patients, many apparent increases in cholesterol level may be false positive. Independent of the office visit schedule, the interval for monitoring patients who are receiving stable cholesterol-lowering treatment could be lengthened.