A groundbreaking study from The Lundquist Institute, published in the Journal of the American College of Cardiology: Advances on April 7, 2025, challenges the long-standing belief that high cholesterol levels, specifically elevated LDL cholesterol (LDL-C) and apolipoprotein B (ApoB), are direct indicators of heart disease risk, particularly in metabolically healthy individuals. The research highlights the need for more personalized cardiovascular risk assessments, especially for those following low-carbohydrate ketogenic diets.
The study focused on 100 metabolically healthy individuals following a long-term low-carb ketogenic diet, known as Lean Mass Hyper-Responders (LMHRs). These individuals exhibited elevated LDL-C levels despite having other positive metabolic markers such as low triglycerides, high HDL cholesterol, low blood pressure, low insulin resistance, and low body mass index.
Contrary to the prevailing lipid hypothesis, which suggests that high levels of LDL-C and ApoB are significant risk factors for cardiovascular disease, the study found no correlation between elevated cholesterol levels and the progression of coronary artery disease (plaque buildup). The researchers concluded that high cholesterol may not always signal increased heart disease risk in metabolically healthy people.
The strongest predictor of plaque progression was identified as baseline plaque burden, not cholesterol levels. This suggests that in individuals with the LMHR phenotype, other factors, such as pre-existing plaque levels, may be more critical indicators of cardiovascular risk.
The study calls for personalized approaches to cardiovascular risk assessment, including the use of cardiac imaging for LMHR individuals, as their high cholesterol levels may not necessarily correlate with heart disease progression.
Context and Implications:
Cardiovascular disease remains the leading cause of death globally, making accurate diagnosis and risk assessment crucial. The study challenges the traditional understanding of lipid-based risk factors, particularly in the context of low-carb ketogenic diets, which are increasingly being used to manage chronic conditions like diabetes, inflammatory bowel disease, and even mental health disorders. Despite the success of these diets, they are often discouraged by healthcare professionals due to concerns over their potential to raise cholesterol and increase heart disease risk.
The findings emphasize the importance of individualized treatment strategies and risk assessments, taking into account factors beyond just cholesterol levels. As more evidence mounts regarding the benefits of low-carbohydrate diets, particularly for people with chronic health conditions, it becomes clear that cholesterol may not always be a reliable marker of cardiovascular risk in metabolically healthy individuals.
Conclusion:
This study underscores the need for a shift in how we assess cardiovascular disease risk, especially for individuals following ketogenic or low-carb diets. With more research, personalized, data-driven approaches that include advanced imaging and alternative markers of metabolic health could lead to better, more accurate cardiovascular assessments.
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