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

Over the last 100 years, the idea that high LDL cholesterol (LDL-C) leads to heart disease has been deeply ingrained in both public health guidelines and clinical practice. From Ancel Keys’ early research to the rise of statins in the 90s and 2000s, the focus has been on lowering LDL-C at all costs.

But recent research is starting to challenge this narrative, offering new perspectives on metabolic health and cholesterol.

The last 100 years of cholesterol recommendations:

For much of the 20th century, the lipid hypothesis dominated, claiming a direct relationship between dietary fats, cholesterol levels, and heart disease. Statins and guidelines focused heavily on lowering LDL-C as the primary strategy to reduce cardiovascular risk. However, newer studies are questioning whether LDL-C alone tells the full story—especially in metabolically healthy individuals.

A recent study, “Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial”, challenges the conventional wisdom. It found that elevated LDL-C and ApoB were not linked to the progression of coronary artery disease in a group of metabolically healthy individuals on a ketogenic diet. This suggests that LDL-C levels may not always correlate with cardiovascular risk, especially when other factors like inflammation and insulin resistance are considered.

What does this mean for cholesterol and heart disease?

The findings support a more personalized approach to cardiovascular risk management, emphasizing metabolic health over just cholesterol numbers. The presence of plaque in the arteries (i.e., existing atherosclerosis) is a stronger predictor of future heart disease than LDL-C levels alone, especially in individuals who are lean and metabolically healthy.

The shift from old guidelines to emerging views:

Old View	Emerging View
LDL-C is inherently harmful	Context matters: metabolic health modifies risk
Lower is always better	Lower may not be necessary for all
Statins for most, just in case	Stratify by risk and metabolic profile
High LDL = high risk	High LDL + low inflammation + no plaque ≠ high risk

What’s next?

While the study doesn’t absolve LDL-C from being a critical marker of risk in some populations, it calls for more nuanced and individualized approaches to health. As we move forward, it’s crucial to consider not just cholesterol but also the underlying metabolic state of the individual.

This growing body of evidence suggests that insulin sensitivity, inflammation, and lifestyle factors may be just as—or more—important than focusing solely on lowering LDL-C levels. It's time to rethink what truly matters for heart health.