Biomarker variability and cardiovascular disease residual risk

A number of cohorts and clinical trials have reported observing associations between intraindividual variation of biomarkers and manifestations of cardiovascular disease (CVD).

Intraindividual (or 'visit-to-visit') variability of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglyceride have all been found to associate with CVD outcomes, independent of their mean absolute levels, independent of each other, and independent of other traditional risk factors. These findings have been confirmed recently in large cohort studies in different populations, and in post-hoc analyses of clinical trial data. Lipoprotein variability has been associated with myocardial infarction, other arterial disease including cerebrovascular, and with cardiovascular and overall mortality. The association of higher variability of LDL-C with atheroma progression has also been assessed directly using intravascular ultrasound and carotid intima-media thickness. The lipoprotein variability of an individual contributes to their residual risk of CVD, although the mechanism remains unclear.

There is compelling evidence that lipoprotein variability contributes to residual risk; however, a more standardized approach is required before the risk attributable to variability can be assessed effectively.