Greater Cholesterol Variability Is a Predictor for Atheroma Progression

Ahmed Younes, M.D.
By Ahmed Younes, M.D. on

“The variation in cholesterol levels is associated with an increase in the percentage of atheroma volume and worse clinical outcomes,” says a new meta-analysis in the European Heart Journal.

Visit-to-visit low-density lipoprotein cholesterol (LDL-C) variability has recently aroused interest as a possible predictor of cardiovascular events, in the field of cardiovascular prevention. Previous studies have shown an association between the low-density lipoprotein cholesterol (LDL-C) variation and the adverse clinical outcomes. However, in this study, the authors aimed to evaluate if there was an association between intra-individual lipid variability and coronary atheroma progression. 

Dr. Rishi Puri, the Interventional Cardiologist and the Director of Atherosclerosis Imaging Lab at Mayo Clinic commented, “Several recent studies in primary and secondary prevention cohorts have demonstrated that higher intra-individual cholesterol variability is associated with adverse clinical outcomes. The prognostic importance of visit-to-visit variability appears significant; however, mechanisms underlying this association are not well known. Whether higher cholesterol variability is merely reflective of a broader systemic phenomenon or directly related to a pro-atherosclerotic process remains unexplored.”

“We found that higher visit-to-visit cholesterol variability is significantly associated with progression in plaque volume and adverse cardiovascular outcomes.” – Dr. Rishi Puri

This study included about 5,000 patients from nine previous trials who had serial coronary intravascular ultrasonography (IVUS). The authors assessed if there is an association between the progression of atheroma volume (PAV) and the variation in the cholesterol levels. The lipid panel included low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), total cholesterol (TC), non-high-density lipoprotein (non-HDL-C), high-density lipoprotein (HDL-C), and apolipoprotein B (apoB).

The analysis demonstrated the role of variability in atherogenic lipoproteins in PAV. Variability in LDL-C, non-HDL-C, TC/HDL-C AND apo-B non-HDL-C, TC/HDL-C and apt B was significantly associated with PAV. However, there was no relationship between HDL-C variability and PAV. The results of this analysis supported the role of variability not only with LDL-C but also other atherogenic lipoproteins. When levels of LDL-C, non-HDL-C and Apo-B were discordant, TC/HDL-C was found to accurately identify atheroma progression and may better reflect atherogenic lipid particles. This study highlighted both the importance of aggressive lowering of atherogenic lipoprotein levels and achieving stable reductions.

When asked to comment on the results of the study, Dr. Puri said, “Our study utilizes serial intravascular ultrasonography measurements, which allows for precise quantification of coronary plaque volume over time. We found that higher visit-to-visit cholesterol variability significantly associates with progression in plaque volume and adverse cardiovascular outcomes. These findings are important because it suggests that greater cholesterol variability is a pro-atherosclerotic process. Our results were consistent across a range of atherogenic lipoproteins including total cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol ratio, and apolipoprotein B. Importantly, achieved levels of atherogenic lipoprotein levels demonstrated a comparatively stronger relationship with plaque progression, highlighting the importance of targeting low lipoprotein levels.”

This analysis is limited to patients enrolled in clinical trials with an indication for coronary angiography and may not be applicable to those without documented atherosclerotic heart disease.

When asked about the implications of this study in the clinical practice, Dr. Puri commented, “Our findings support targeting low and consistent atherogenic lipoprotein levels. This is important to consider as new agents, such as PCSK9 inhibitors, become more widely used. Additionally, utilizing periodic monitoring of lipid levels to assess variability may be important to identify patients at higher risk of adverse cardiovascular outcomes. Further research is needed to understand therapeutic implications and how cholesterol variability incorporates into clinical practice.”


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