Cholesterol Shock:
Why Too Much 'Good' Can Be Bad
Cholesterol. It's a word that sparks concern, especially when we talk about heart health. For years, we’ve been told that keeping cholesterol levels low is the key to a healthy heart and a long life. But recent studies have unveiled a surprising twist: both low and high levels of cholesterol can be harmful.
First, let’s break down cholesterol into its two main types:
Low-Density Lipoprotein (LDL): Often dubbed "bad" cholesterol, LDL can accumulate in your arteries, leading to blockages that increase the risk of heart attacks and strokes.
High-Density Lipoprotein (HDL): Known as "good" cholesterol, HDL helps remove LDL from your bloodstream, transporting it to the liver for disposal. Higher levels of HDL are traditionally seen as protective against heart disease.
A groundbreaking study published in 2017 in the European Heart Journal took a deep dive into those “good” HDL cholesterol levels. They analyzed data from two major Danish population studies involving over 116,000 participants. Their findings turned conventional wisdom on its head.
The study revealed a U-shaped relationship between HDL cholesterol levels and mortality. They found that both very low and very high levels of HDL cholesterol are associated with increased mortality risk.
Low HDL Levels: Men with HDL cholesterol levels below 1.0 mmol/L (39 mg/dL) and women with levels below 1.0 mmol/L had a significantly higher risk of dying from any cause.
Optimal HDL Levels: The lowest mortality risk was found at HDL levels of 1.9 mmol/L (73 mg/dL) for men and 2.4 mmol/L (93 mg/dL) for women.
High HDL Levels: Surprisingly, extremely high HDL levels were also linked to higher mortality. Men with HDL levels of 2.5–2.99 mmol/L (97–115 mg/dL) and women with levels of 3.0–3.49 mmol/L (116–134 mg/dL) faced increased risk.
Very High HDL Levels: For men with HDL levels of 3.0 mmol/L (116 mg/dL) or higher, and women with levels of 3.5 mmol/L (135 mg/dL) or higher, the risk was even more pronounced.
Adding another layer of complexity, a 2023 study titled "Association of Plasma High-Density Lipoprotein Cholesterol Level with Risk of Incident Dementia" examined HDL levels in relation to dementia risk in healthy older adults. The study found that both low and high HDL levels were associated with an increased risk of developing dementia, echoing the U-shaped risk curve observed in mortality studies.
Why would both low and high HDL cholesterol levels be dangerous? Here are some possible explanations:
Genetic Factors: Extremely high HDL levels might be influenced by genetic mutations that also increase the risk of other health issues, such as cardiovascular disease. For example, mutations in genes like CETP, ABCA1, and SCARB1 can lead to high HDL levels but also higher disease risk.
Functional Quality of HDL: HDL is more than just a number. The quality and functionality of HDL particles matter. Extremely high levels might indicate dysfunctional HDL that doesn’t perform its protective roles effectively.
Underlying Health Conditions: Individuals with very high HDL levels might have underlying health conditions that contribute to higher mortality and dementia risks, separate from the cholesterol itself.
Lifestyle and Socioeconomic Factors: Lifestyle factors such as smoking, alcohol consumption, physical inactivity, and socioeconomic status are closely linked to HDL levels and overall health outcomes.
CETP (Cholesteryl Ester Transfer Protein): Mutations reducing CETP activity can raise HDL levels but also increase cardiovascular disease risk.
ABCA1 (ATP-Binding Cassette Transporter A1): Certain variants in ABCA1 can result in very high HDL levels but may be linked to other health complications.
SCARB1 (Scavenger Receptor Class B Type 1): Loss-of-function mutations in SCARB1 can elevate HDL levels but have been associated with higher coronary heart disease risk.
So, what does this mean for you, someone looking to live a longer, healthier life? Here are some takeaways:
Balanced Cholesterol Management: Aim for balanced cholesterol levels rather than focusing solely on pushing you “good” HDL higher. Both extremes can be harmful.
Holistic Health Approach: Consider a broader range of health factors, including genetics, lifestyle, and overall wellness, rather than just cholesterol numbers.
Personalized Health Plans: Work with your healthcare provider to develop a personalized plan that considers your unique health profile and risks.
Stay Informed: Keep up with the latest research and understand that health recommendations can evolve as new discoveries are made.
The relationship between cholesterol and health is more nuanced than we once thought. While maintaining healthy cholesterol levels is important, it's crucial to avoid extremes.
Reference Links:
Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults
Sultana Monira Hussain, Catherine Robb, Andrew M. Tonkin, Paul Lacaze, Trevor T.-J. Chong, Lawrence J. Beilin, Chenglong Yu, Gerald F. Watts, Joanne Ryan, Michael E. Ernst, Zhen Zhou, Johannes T. Neumann, John J. McNeil
The Lancet, Published November 29, 2023DOI:https://doi.org/10.1016/j.lanwpc.2023.100963
High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular Conditions: The CANHEART Study
Dennis T. Ko MD, MSc, David A. Alter MD, PhD, Helen Guo MSc, Maria Koh MSc a, Geoffrey Lau BHSc candidate, Peter C. Austin PhD, Gillian L. Booth MD, MSc, William Hogg MD, MCISc, Cynthia A. Jackevicius PharmD, MSc, Douglas S. Lee MD, PhD, Harindra C. Wijeysundera MD, PhD, John T. Wilkins MD, Jack V. Tu MD, PhD
Journal of the American College of Cardiology, Published: Received 12 July 2016, Accepted 9 August 2016, Available online 31 October 2016, Version of Record 31 October 2016.
Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies
Christian M. Madsen, Anette Varbo, Børge G. Nordestgaard
European Heart Journal, Published 12 April 2017
Everything in Moderation: Investigating the U-Shaped Link Between HDL Cholesterol and Adverse Outcomes
Marc P Allard-Ratick, Pratik Sandesara, Arshed A Quyyumi and Laurence S Sperling
USC US Cardiology Review, Published online:12 March 2019
Call for a FREE Consultation (305) 296-3434
CAUTION: Check with your doctor before
beginning any diet or exercise program.
7/27/2024
Updated 7/30/2024
