Is LDL Cholesterol Really the Bad Guy? New Research Challenges Decades of Heart Disease Advice. PART 2

The findings from the study "Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial" have sparked both interest and criticism, especially regarding the absence of a proper control group.

While this research provides valuable insights into the relationship between LDL-C and coronary artery disease, there are significant gaps in how we interpret these results—gaps that could be addressed with further studies. Specifically, the lack of a control group with low LDL-C levels leaves many questions unanswered. This gap, along with the study’s limitations, highlights why we need to remain curious and cautious as new findings continue to emerge.

The missing control group: Why does it matter?

In the KETO-CTA trial, researchers found that LMHRs experienced plaque progression over time, raising concerns about the long-term cardiovascular risks of elevated LDL-C, even in seemingly healthy individuals. The study reported an 18.8 mm³ increase in non-calcified plaque volume over the course of one year. While this might sound alarming, the absence of a control group with low LDL-C levels makes it impossible to draw any meaningful comparisons.

Without a control group of individuals with low LDL-C levels, we lack a baseline to evaluate whether the observed plaque progression is typical or whether it is uniquely linked to the high LDL-C levels in LMHRs. A control group is essential to understanding whether high LDL-C truly causes accelerated plaque buildup or if other factors (such as genetics, lifestyle, or pre-existing conditions) are at play.

Furthermore, a control group could help assess the magnitude of plaque progression and its implications. Are individuals with low LDL-C also experiencing plaque progression, but at a slower rate? Or does the absence of elevated LDL-C result in minimal plaque progression? Without these crucial comparisons, it is difficult to make conclusions about the safety of high LDL-C, even in those who are otherwise metabolically healthy.

Understanding the heterogeneity of results: The need for further study

The heterogeneity of results in studies like the KETO-CTA trial cannot be overlooked. The observed variation in plaque progression among different individuals—some with significant plaque growth and others with little to no change—suggests that there may be multiple factors influencing cardiovascular risk beyond just LDL-C levels. These factors could include genetics, diet, exercise habits, stress levels, and pre-existing cardiovascular conditions.

As the study’s authors note, ongoing research is needed to better understand these variations and identify the precise mechanisms at play. With future studies on the way, it is critical that we continue exploring how LDL-C behaves in different populations—especially those with differing genetic backgrounds, dietary patterns, and health statuses. A deeper understanding of these factors will help paint a more complete picture of how and why certain individuals may be more susceptible to plaque formation than others.

If we fail to account for the heterogeneity of these findings, we risk oversimplifying complex cardiovascular risks and potentially misguiding individuals who are at different stages of health. This is why studies with diverse populations and varied risk factors are crucial to help identify who might truly be at risk and who can safely maintain higher levels of LDL-C.

Until then, we must remain curious, continue asking critical questions, and look forward to further research that will allow us to refine our understanding of LDL-C, plaque progression, and cardiovascular health. In science, there are always more questions than answers, and it is this curiosity that will ultimately lead us to a deeper understanding of our health.