Debunking Common Cholesterol Myths

Cholesterol has been a subject of debate in cardiovascular health. Despite its crucial role in various bodily functions, questions persist about its association with atherosclerotic cardiovascular disease (ASCVD).

What is cholesterol?

Cholesterol is a waxy, fat-like substance found in every cell of the body, essential for producing hormones, vitamin D, and substances that help digest foods. It is transported through the bloodstream by lipoproteins, which are composed of fat on the inside and proteins on the outside. There are two primary types of lipoproteins:

• Low-density lipoprotein (LDL): Often referred to as "bad" cholesterol, carries cholesterol from the liver to the cells. If too much LDL cholesterol circulates in the blood, it can slowly build up in the walls of the arteries, forming plaques that can narrow or block blood flow, leading to atherosclerosis and increasing the risk of heart disease and stroke.
• High-density lipoprotein (HDL): Known as "good" cholesterol, helps remove excess cholesterol from the bloodstream, transporting it back to the liver for processing and excretion. This balance between LDL and HDL is crucial for maintaining cardiovascular health.

Understanding the basics of cholesterol is essential before we delve into common myths and misconceptions.

Debunking Common Cholesterol Myths

Myth #1: Cholesterol does not play a role in ASCVD

The lipid/cholesterol hypothesis suggests that high levels of LDL cholesterol play a central role in the development of ASCVD. This is supported by a wide variety of clinical evidence accumulated for over a century.

In 1913, Nikolaj Anitschkow set the groundwork for the lipid hypothesis^[1]. Anitschkow's work involved feeding cholesterol to rabbits and then observing the effects of this diet on the arteries of the rabbits. Anitschkow found that the rabbits fed with cholesterol developed artery-clogging plaques, similar to those found in humans with heart disease. This discovery was the first evidence that linked dietary cholesterol to development of atherosclerosis, a primary underlying cause of heart disease.

But it's not just about rabbits; the result of this study applies to humans too. Over the years, research in humans has confirmed what Anitschkow found: high cholesterol levels are linked to a higher risk of heart disease.

The Framingham Heart Study^[2] began in 1948 and is now on its third generation of participants. It has been pivotal in understanding cardiovascular risk factors. Using epidemiological and genetic techniques, this long-term study has demonstrated a clear association between elevated LDL levels and increased risk of heart disease. The study's comprehensive data collection and analysis have significantly influenced public health guidelines and cholesterol management strategies.

Additionally, physiologist Ancel Keys’ epidemiological work^[3] in the 1950s helped solidify the lipid hypothesis. He observed a correlation between dietary fat intake and blood cholesterol levels in populations around the world. He was able to determine that in societies where dietary fat was a major component of every meal, such as in the US, both blood cholesterol levels and heart disease death rates were highest. Conversely, in cultures with diets rich in fresh fruits and vegetables, bread, pasta, and olive oil, such as the Mediterranean region, blood cholesterol levels were low and heart disease was rare.

Modern clinical data continues to support these early findings. The INTERHEART study^[4] highlighted the significance of lipids in myocardial infarction risk across different populations globally. It demonstrated that abnormal lipid levels, particularly high LDL cholesterol, are one of the most important risk factors for heart attacks.

In conclusion, the evidence overwhelmingly supports the role of cholesterol in the development of ASCVD. High levels of LDL cholesterol are a well-established risk factor, and managing these levels is essential for cardiovascular health.

Myth #2: Cholesterol-lowering treatment does not lower the risk of ASCVD

Clinical trials and extensive research have shown that lowering LDL cholesterol levels reduces the risk of ASCVD^[5]. Statins, a class of drugs that lower cholesterol levels, have been proven to significantly decrease the incidence of heart attacks and strokes by up to 20-30%^[6].

The Scandinavian Simvastatin Survival Study (4S)^[7] demonstrated that lowering LDL cholesterol with statin therapy significantly reduced the incidence of heart attacks and strokes in high-risk individuals. In this study, simvastatin reduced total cholesterol by 25% and LDL cholesterol by 35%, which resulted in a 34% reduction in major coronary events and a 30% reduction in all-cause mortality over five years.

Similarly, the Heart Protection Study (HPS)^[8] provided evidence supporting the benefits of cholesterol-lowering treatments in reducing cardiovascular events. The HPS, which involved over 20,000 participants, showed that simvastatin reduced the risk of heart attacks, strokes, and revascularization procedures by about 25% even in individuals with no prior history of heart disease, reinforcing the preventive benefit of statin therapy.

Myth #3: High cholesterol levels are only a concern for older adults

Elevated cholesterol levels pose a threat across all age groups, including younger individuals. Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated LDL cholesterol levels, exemplifying how high cholesterol can afflict individuals from a young age and cause premature ASCVD. Furthermore, the onset of atherosclerosis in youth underscores the importance of addressing cholesterol levels from an early age to reduce the risk of cardiovascular complications. Lifestyle modifications, such as adopting a heart-healthy diet, and engaging in regular physical activity are important interventions for cholesterol management in both younger and older populations^[9].

Myth #4: Only LDL cholesterol levels matter

While LDL cholesterol is a significant factor in heart disease, it's not the only one that matters. HDL cholesterol, triglycerides, and other lipid particles also play important roles in cardiovascular health. The Framingham Heart Study^[2] found that low levels of HDL cholesterol were associated with an increased risk of coronary heart disease, independent of LDL cholesterol levels. Additionally, elevated triglyceride levels have been linked to a higher risk of cardiovascular events, as shown in the Copenhagen City Heart Study ^[10]. A comprehensive approach to lipid management, including lowering LDL, raising HDL, and managing triglycerides, is crucial for reducing overall cardiovascular risk.

Myth #5: If high LDL-C is the major cause of ASCVD, then people with the highest LDL-C values would have shorter lives than people with lower values

Ravnskov et al.,^[11] looked at 19 existing studies which considered the association between LDL-C levels and the overall risk of death in people aged over 60. The authors reported a statistically significant inverse association between all-cause death and LDL-C levels and concluded that their findings question the validity of the prevailing cholesterol hypothesis and provide rationale for a re-evaluation of guidelines that recommend reducing LDL-C levels in the elderly as a component of cardiovascular disease prevention.

However, this interpretation has been met with significant criticism. Critics argue that the inverse association observed by Ravnskov could be due to several factors, including reverse causation, where individuals with serious illnesses often have lower cholesterol levels due to their condition or treatments. Additionally, frailty and malnutrition in the elderly can lead to lower cholesterol levels, complicating the direct relationship between LDL-C and mortality^[12].

In contrast, extensive longitudinal studies, such as the Framingham Heart Study^[2], provide robust evidence supporting the role of high LDL-C in increasing ASCVD risk. Duncan et al.,^[13] analyzed the Framingham cohort over 35 years and identified distinct LDL-C trajectory groups. Their findings showed that individuals with consistently elevated LDL cholesterol levels throughout life experienced significantly higher rates of ASCVD and all-cause mortality compared to those with optimal or declining LDL cholesterol levels.

Conclusion

Despite the abundance of evidence linking cholesterol to ASCVD, myths and misconceptions persist. Understanding the facts about cholesterol and its impact on cardiovascular health is crucial for making informed decisions about managing your health. By debunking these common myths, we can better appreciate the importance of cholesterol management in preventing heart disease and promoting overall well-being.