Physicians' Academy for Cardiovascular Education

Higher cholesterol variability associated with increased incidence of CV outcomes

Cholesterol variability and the risk of mortality, myocardial infarction, and stroke: a nationwide population-based study

Kim MK, Han K, Kim H-S, et al. - Eur Heart J 2017;38:3560–3566


Existing data from small studies suggest that a high visit-to-visit variability in cholesterol levels is an independent predictor of MACE in high-risk CAD patients [1,2]. However, the prognostic significance of cholesterol variability in the general population is unknown.

In this large population-based study of 3,656,648 individuals, the prognostic significance of increased total cholesterol (TC) variability on all-cause mortality, MI, and stroke was evaluated. For this purpose, Koreans aged ≥20 years without previous MI or stroke enrolled in the National Health Insurance System [3,4], with at least 3 TC measurements between January 1, 2002 and December 31, 2007, were followed-up for a median of 8.3 years. TC variability was calculated based on 3 indices:

The study endpoints were newly-diagnosed MI, ischemic stroke, or death.

Main results


In a large population-based cohort study, TC variability was an independent predictor for the development of MI and stroke, as well as for all-cause mortality in the general population. These data suggest that reducing TC variability may be of benefit in the primary prevention of CVD.

Editorial comment

In his editorial article, Bangalore [5] notes that intra-individual variability in hemodynamic factors, such as blood pressure, is a sign of life. He raises a number of open questions related to the association between cholesterol variability and clinical outcomes as studied by Kim et al. He first questions whether the association is causal or merely a bystander-effect, and does this in the context of Hill’s 9 criteria for causation [6]. Although many of the criteria are satisfied, Bangalore concludes that the causality of the relationship is far from perfect. He then discusses practical difficulties, like the lack of measures and cut-offs for cholesterol variability. He concludes: ‘Moreover, the clinical implications are not known. At present, increased variability may represent potential medication noncompliance and, if not, perhaps consideration should be given to use a high-intensity statin given data showing reduced cholesterol variability. However, it is not known if reducing cholesterol variability will indeed impact prognosis. Before any of these are incorporated into clinical practice, more studies are needed to test whether this is ‘causal’ or merely an epidemiological association.’


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Find this article online at Eur Heart J