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 studyLiterature - Kim MK, Han K, Kim H-S, et al. - Eur Heart J 2017;38:3560–3566
- Participants were divided into quartiles according to their TC variability. The mean TC levels were ~190 mg/dL in all groups, with increasing CV values in ascending quartiles (Q1: 4.25±1.36%; Q2: 7.48±0.77%; Q3: 10.38±0.97%; Q4: 16.78±4.65%).
- The incidence rate of all-cause mortality increased stepwise with higher CV quartiles of TC variability.
- The association between TC variability and all-cause mortality remained significant after adjustment for baseline characteristics (HR for Q2: 1.03; 95% CI: 1.00-1.05; HR for Q3: 1.08; 95% CI: 1.06-1.10; HR for Q4: 1.26; 95% CI: 1.24-1.28, as compared with Q1).
- Similar to the outcome of all-cause mortality, an incrementally higher risk of MI and stroke was observed with higher CV quartiles compared with the lowest quartile group in all models adjusting for baseline characteristics.
- Individuals in the CV of TC variability Q4 group had an approximately 8% higher risk of MI and 11% higher risk of stroke compared with the CV Q1 group.
- The results were consistent when the TC variability was determined using SD and VIM, and TC variability measured by SD or VIM was an independent predictor of all-cause mortality, MI, and stroke even after full multivariable adjustment.
- When the variability index was used as a continuous variable, a 5% increase in CV was associated with a significantly increased risk of outcomes after full multivariable adjustment (HR for all-cause mortality: 1.09; 95% CI: 1.08–1.09; HR for MI: 1.03; 95% CI: 1.02–1.04; HR for stroke: 1.03; 95% CI: 1.03-1.04).
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.
In his editorial article, Bangalore  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 . 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.’