The LDL Cholesterol Debate

One of the great controversies in recent decades is what level of LDL cholesterol is associated with the lowest risk of occlusive arterial disease (atherosclerosis).¹

Those with a genetic propensity to over-produce cholesterol suffer premature atherosclerosis and increased cardiovascular disease incidence.^2,3

This undisputed fact has been used to help support the importance of lowering very high LDL cholesterol.

The debate centers around what constitutes "optimal" LDL blood levels for normal and high-risk individuals.

With age, LDL often elevates to ranges that cause or contribute to arterial blockages.^4,5

This is concerning because atherosclerosis remains the leading cause of disease, disability, and death in the United States.⁶

I am aware of different positions that well informed people take on the "LDL Cholesterol Debate".

The data presented in this editorial reflect views of those who argue for lower LDL blood levels to reduce atherosclerotic-induced disorders.

Options for achieving safer LDL blood levels are provided.

Differences in opinion about "optimal" LDL cholesterol values have caused fierce debate for many decades.

While clear consensus remains elusive, a recent review paper argues that based upon all current evidence, the LDL level to prevent atherosclerosis should be lower than commonly advocated.⁷

The authors of the review suggest targeting LDL to as low as 40 mg/dL for patients at highest risk. This is similar to the LDL level of newborn infants.

These authors acknowledge that these low LDL levels will be challenging to achieve and may not be feasible for all patients without use of LDL-reducing drugs.

For patients with no significant additional risk factors for cardiovascular disease, the authors suggest that keeping LDLbelow 85 mg/dL from birth throughout life would likely delay onset of atherosclerosis complications until age 100 yearsor more.⁷

This conflicts with what some in the alternative and conventional medical communities recommend. Yet there are data to argue that LDL is a "vascular toxin."⁷

The authors point to mathematical modeling of observational data that suggests atherosclerosis risk is lowest at an LDL level of around 38 mg/dL.

Current LDL cholesterol guidelines vary between European and American experts, as well as among different expert working groups within different countries.

The current consensus generally suggests LDL blood levels should be below 100 mg/dL in healthy individuals and below 70 mg/dL in people at high coronary risk.

I'll describe how these new "lower" LDL recommendations apply later in this article.

Modern-day Achilles Tendon

Cardiovascular diseases are the greatest threats to our healthy longevity.

We at LifeExtension® have long advocated that more needs to be done to prevent and treat atherosclerosis.

Arterial/vascular disease not only causes heart attacks and ischemic strokes, but also contributes to:

• Several types of Dementia^8-10
• Peripheral arterial disease^11-13
• Heart failure^13-15
• Renal artery stenosis^11,16,17
• Carotid artery stenosis and embolization¹⁸
• Kidney failure¹⁹
• Hypertension²⁰
• Aortic calcification/stenosis²¹
• Mesenteric artery disease²²
• Erectile dysfunction^23-25
• Frailty^26,27
• Accelerated aging²⁸

Arterial disease represents our greatest vulnerability. It's an Achilles tendon to our continued existence.

Treating Atherosclerosis More Aggressively!

A review article published December 2022 in the American Journal of Preventive Cardiologymade provocative arguments for achieving very low LDL blood levels.

For those who don't want to read this full-text document, I summarize the following salient points:⁷

• Atherosclerosis is a preventable disease.
• Elevated LDL is a necessary factor for atherogenesis induction.
• Observational data from retrospective analyses, prospective longitudinal data, and interventional randomized clinical trials support LDL as a significant risk factor for atherosclerosis.
• The percentage of high- and very high-risk patients who achieve optimized LDL target reductions is low and has remained low for the last 30 years.
• The majority of patients at atherosclerotic risk are inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging.
• The relationship between LDL cholesterol and risk for atherosclerotic cardiovascular disease is one of the most highly established/investigated issues in the entirety of modern medicine.

The above bullet points may enlighten some of you, while causing disagreement amongst others.

I next describe the most controversial aspect of this December 2022 published review.⁷

Optimal LDL Blood Levels: “20-40 mg/dL”?

The authors of this 2022 review argue that the optimal LDL appears to be the level present at birth (20–40 mg/dL). They also recognize that that this range is probably not necessary for everyone nor practical to attain widely.

These authors suggest that LDL below 40 mg/dL seems the most effective goal for patients in the category of more advanced atherosclerosis, i.e., vascular disease patients at highest risk.

Recall that the current target advocated by many lipid authorities, but not all, for those at high cardiovascular risk is LDLbelow 70 mg/dL.

What you've read so far represents quite a difference of opinion! Especially when today's general recommended LDL reference range is somewhere below 100 mg/dL.  

To put this in historic perspective, in the 1980s the upper limit for LDL readings was around 160 mg/dL,²⁹ which is considered high by today's standards.

We at Life Extension® argued back then that LDL blood levels should be below 100 mg/dL. Subsequent research helped validate this, yet there is now published data to suggest even lower LDL targets.

DATA SUPPORTING LOWER LDL LEVELS

The authors of the December 2022 review cite the following data to argue that today's LDL reference ranges are too high:

• Animals and humans who maintain low cholesterol levels early in life have very little atherosclerosis.
• Very low LDL levels are observed among hunter-gatherer populations who have less evidence of atherosclerotic disease.
• The LDL level where there is no excess risk of atherosclerotic cardiovascular disease is approximately 38 mg/dL. (This is strikingly low by most current standards.) 
• Over a 26.5- year follow-up, even baseline LDL under 100 mg/dL resulted in a continuous rise in risk for coronary heart disease mortality. (This suggests the importance of targeting LDL lower than current standards.)^30,31
• Average LDL level of men presenting with an acute coronary syndrome is approximately 150 mg/dL.³² (This LDL level was viewed as "normal" in the 1980s when heart attack rates were higher.)
• These lower LDL levels are difficult to achieve in a modern society and may not be necessary for people not at high cardiovascular disease risk.
• Unfortunately, aging itself is the greatest coronary artery disease risk factor.³³
• In addition, most of us have had exposure to secondhand tobacco smoke and less than ideal dietary practices in our early years. This inflicts arterial damage that can manifest as cardiovascular disease in later life.
• One way to reduce cardiovascular risk is to target LDL to lower ranges depending on individual circumstances.

LDL-Lowering Strategies

Decreasing intake of saturated fat (meat, butter, cheese, and full-fat dairy) to less than 7% of daily calorie intake can reduce LDL by 8% to 10%.³⁴

The problem is that a typical aging person's LDL is far above 120 mg/dL.

Even if they stick with a rigid diet, a 10% decrease translates into an LDL level of 108 mg/dL, which may be twice as high as ideal for many individuals.

Statin drugs have been attacked by alternative medicine for decades. Yet the side-effect risks of modest statin drug dosing may be trivial compared to the deadly impact of elevated LDL and related lipids like apolipoprotein B (ApoB).^35,36

Dangerously high levels of ApoB occur commonly in people with high LDL.³⁷ The statin drug rosuvastatin was shown to reduce ApoB levels by 36%-45%, which was better than other statin drugs tested.³⁸

Life Extension® Magazine published an article in 2003 showing that every other day dosing of a modest statin (10 mg/atorvastatin) yielded significant benefits with zero side effects. And for some of you, a modest statin dose taken every other day might push your LDL down to an ideal range.³⁹

Those with higher LDL levels may take a modest dose statin combined with another drug (ezetimibe) that blocks intestinal reabsorption of cholesterol.⁴⁰ Others need a higher dose statin drug to achieve LDL below 40 -70/mg/dLdepending on their cardiovascular risk factors.

An expensive class of drugs (PCSK-9 inhibitors) such as Repatha® can slash LDL to below 30 mg/dL. Insurance companies often refuse to pay the high price of this drug.^41,42

I am aware of the concerns raised about statin drug side effects. Overlooked by many, however, is the ability of statin drugs to lower elevated LDL and ApoB.

There has been a multi-decade debate about what optimal LDL blood levels should be. As it relates to the dangers of elevated ApoB, there is virtual unanimity, i.e., keep your ApoB levels in low ranges to reduce atherosclerotic risks.

A Non-Drug Approach!

An article on page 36 of this month's issue describes a botanical extract that has demonstrated LDL-lowering effects.

The latest human study showed a 21.8% decline in LDL. The placebo arm of this study had a 3.83% LDL increase.⁴³

In addition to reduced LDL, this plant extract was shown to lower total cholesterol, triglycerides, and C-reactive protein* while boosting beneficial HDL.

These favorable blood changes were accompanied by improved endothelial function, a measure of arterial health.

For many readers of Life Extension® Magazine, a 21% reduction in LDL will achieve desired levels. Others might need a statin drug in addition to this plant extract to achieve optimal LDL ranges.

*C-reactive protein is a marker of chronic inflammation. Elevated C-reactive protein has been shown in some studies to be a greater cardiovascular risk factor than high LDL cholesterol.⁴⁴

INTERESTING MAPS

The maps copied on this page show an association of high cholesterol prevalence and increased incidence of strokeand lower life expectancy.

While these maps show correlation and not causation, they depict shorter lifespans in areas where most people fail to take care of their health.

Map A shows that concentrations of counties with the highest cholesterol prevalence—meaning the top quintile—are located primarily in Mississippi, Louisiana, Arkansas, Oklahoma, Texas, Kentucky, Tennessee, Michigan, Maine, South Carolina, and Kansas.⁴⁶

A.High Cholesterol Prevalence, 2018-2020 Adults Screened, 18+, by County

Source: CDC. https://www.cdc.gov/cholesterol/facts.htm

 

B. Life Expectancy at Birth for U.S. States and Census Tracts, 2010-2015⁴⁷

Source: CDC. https://www.cdc.gov/surveillance/blogs-stories/life-expectancy.html

 

C. Stroke Death Rates, 2018-2020 Adults, Ages 35+, by County⁴⁸

Source: CDC. https://www.cdc.gov/stroke/facts.htm

 

D. Life Expectancy in the U.S. in 2020⁴⁹
Nine-Year Disparity in Human Longevity
(Note lighter colors below reflect reduced life expectancy.)

Source: CDC. https://www.cdc.gov/nchs/pressroom/sosmap/life_expectancy/life_expectancy.htm

Your Blood Test Results are what Matter!

The objective of a lipid-lowering program is to achieve blood levels that have been shown to reduce cardiovascular risks.

Low-cost blood tests provide readings of artery-clogging lipids including LDL, ApoB, and triglycerides.

Current guidelines generally suggest LDL readings over 99 mg/dL are potentially dangerous.

In recent years, those with cardiovascular risks have been advised to drop their LDL to below 70 mg/dL.

A 2022 published review provides evidence that those patients at highest cardiovascular risk may benefit from targeting LDL below 40 mg/dL.⁷

If a blood test reveals higher than optimal LDL or other vascular risk factors, initiate the appropriate corrective action(s). Then retest in a few months to check how the approach works for you.

Assess Your Cardiovascular Risks

The time to lower atherogenic risks is before one suffers a heart attack or ischemic stroke.

I continue to be surprised when asking educated people what their LDL, triglyceride, and C-reactive protein (CRP) levels are. Most respond by saying they have no idea.

I am aware of the different positions that informed people take on the "LDL Cholesterol Debate".

The data presented in this editorial reflect the views of those who argue for lower LDL blood levels to reduce cardiovascular risks.

The blood test panel on the next page costs hundreds of dollars at commercial labs but is available to Life Extension®readers at a steeply discounted price.

The Cardio Core Essentials Panel costs only $68 (item # LC100086) if you order by December 31, 2023.

You can obtain this blood test panel by calling (24-Hours) 1-800-208-3444 or visit: www.LifeExtension.com/CORETEST

For longer life,

William Faloon