William L. Driscoll
Low-density lipoproteins (LDL) in the blood “cause atherosclerotic cardiovascular disease,” says a consensus statement from the European Atherosclerosis Society Consensus Panel.
And high LDL cholesterol was found to be the “strongest modifiable risk factor” for artery-clogging, in a study on early-stage artery clogging published in the Journal of the American College of Cardiology.
It’s helpful to understand the effects of various levels of “bad” LDL cholesterol on your arteries, because maintaining the health of your arteries is vital to a long, healthy life.
This is not doom and gloom—it’s more like “an ounce of prevention is worth a pound of cure.”
LDL cholesterol can be reduced in two ways: by taking on additional healthy lifestyle choices, if possible (see chapter 6), and through treatment with a statin medication, which can dramatically lower LDL (see chapter 7).
This chapter presents medical research findings regarding various levels of LDL cholesterol. Nearly all of the research articles discussed are available free online, through the links provided in the footnotes.
Read the free book on “bad” LDL cholesterol, healthy diets, statin safety, and ultrasound artery screening, at the home page: YourArteries.net
For “bad” LDL cholesterol, “the lower the better”
Five cardiologists and researchers published an influential article concluding that an LDL level below 70 mg/dL is best. Since the article’s publication in 2004 in The Journal of the American College of Cardiology, it has been cited by more than 600 other journal articles.
The authors compiled data showing that LDL cholesterol ranges from 50 to 70 mg/dL for native hunter-gatherers, healthy human newborn children, primates in their natural habitat, and other wild mammals, “all of whom do not develop atherosclerosis.” Data from clinical trials through 2004, the authors wrote, “suggest” that the progression of artery clogging and the likelihood of heart attacks are minimized when LDL is lowered to less than 70 mg/dL.
The article is titled “Optimal low-density lipoprotein is 50 to 70 mg/dL: lower is better and physiologically normal.”
Several years later, three cardiologists and researchers raised the topic again, posing the question “How low should we go?” when helping patients reduce their LDL level. After reviewing the medical literature, they gave their answer in the title of their article: “LDL cholesterol: the lower the better.” The article was published in 2012 in the journal Medical Clinics of North America.
The authors said, based on their literature review, that the “critical role” of lowering LDL cholesterol in reducing cardiovascular risk “is firmly established.” Lowering the LDL level reduces the likelihood of heart attacks and strokes, they said, while slowing and “even inducing regression” of artery clogging.
For “bad” LDL cholesterol, the lower the longer, the better
A lower LDL level beginning early in life results in a “3-fold greater reduction” in the risk of coronary heart disease than lowering LDL to the same level beginning later in life, according to a study by ten researchers published in 2012 in the Journal of the American College of Cardiology.
The researchers reviewed health outcomes for those with genetic variations giving them low lifetime LDL levels, compared to those treated later in life with a statin medication to reduce their LDL level.
Restating the research findings, Dr. Peter Toth, former president of the American Society for Preventive Cardiology, said that the “risk reduction” from lowering LDL cholesterol “is proportional to both the magnitude of the reduction and the duration of time over which this reduction is sustained,” in a 2020 article published in the American Journal of Preventive Cardiology.
“The reticence for treating patients, including young patients, with statins needs to end,” he said.
At LDL cholesterol levels above 40, the risk of coronary heart disease increases at an ever-steeper rate
Nine researchers teamed with the Coordinating Committee of the National Cholesterol Education Program in a study finding that the risk of coronary heart disease rises with increasing LDL levels, and that the rate of increase in risk “rises more steeply” at higher LDL levels. Their review article reached that finding after analyzing five “major clinical trials” of statin therapy whose results were published between 2001 and 2004.
The article, published in the Journal of the American College of Cardiology, has since been cited by 9700 other studies.
For every 30 mg/dL change in LDL, the authors said that “the data suggest” that the relative risk for coronary heart disease is changed in proportion by about 30%.
Preventive cardiologists aim for an LDL cholesterol level as low as 40 in appropriate patients
Preventive cardiologists aim for much lower levels of LDL, in appropriate patients, than the “below 100” level that is widely considered “optimal” for patients without coronary heart disease or diabetes, according to a standard that dates back to 2005. (This guideline from 2005 is referenced to indicate that the continued use of old guidelines may not be appropriate.)
One preventive cardiologist, Dr. Roger Blumenthal, told the author of this book that “moderate” artery clogging—which can be distinguished from mild artery clogging through a “gold standard” carotid artery ultrasound scan (see chapter 5)—”warrants aggressive lipid lowering therapy and comprehensive risk factor reduction.”
Dr. Blumenthal helped this book’s author lower his LDL number to 40, by prescribing a mid-level dose of a statin medication. He said that an LDL level of 40 “is ideal and levels in that range are more likely to result in modest reversal of some of the plaque buildup, as well as stabilization of the plaques throughout your body.”
“Optimal LDL is 50 to 70”
An influential article described earlier in this chapter compiled evidence on the optimal LDL level, and stated its conclusion in the article’s title: “Optimal low-density lipoprotein is 50 to 70 mg/dL: lower is better and physiologically normal.”
At LDL cholesterol levels below 70 mg/dL, modest regression of existing artery-clogging plaque results
A study by 26 co-authors found that the volume of artery-clogging plaque regresses by up to 2% within the first year in study participants whose LDL level was reduced to 70 mg/dL or below. The study was published in 2015 in the Journal of the American College of Cardiology.
The study presented original research comparing the effects of a statin to the effects of a statin plus the drug ezetimibe, and described three previous studies of the effects of a statin alone.
In all four studies, when the LDL cholesterol level was reduced to 70 or below, the plaque volume was reduced by 0.5% to 2% during the study period.
The authors also cited four research trials which showed that “mean LDL cholesterol levels were closely correlated with median change” in plaque volume.
The authors also found that median LDL levels after treatment with a statin plus ezetimibe were about 8 to 15 points lower than after treatment with a statin alone.
An LDL level below 100 mg/dL is not protective against cardiovascular disease
Eight co-authors analyzed data on 136,905 patients hospitalized with coronary artery disease, and concluded that an LDL level below 100 mg/dL is not protective against cardiovascular disease. The study was published in 2009 in the American Heart Journal.
“Almost half” of those patients had an LDL level at the time of hospital admission below 100 mg/dL, the co-authors found.
Coronary artery disease, also called coronary heart disease, is caused by a buildup of plaque in the coronary arteries, which deliver blood to the heart muscle.
The article suggested that a level of “good” HDL cholesterol above 60 mg/dL was protective against cardiovascular disease, as fewer than 10% of those hospitalized for coronary artery disease had HDL above that level.
An LDL level of 115-120 results in 3x higher risk for “adverse outcomes” than an LDL level of 80-90
Three co-authors found that the likelihood of “adverse outcomes” was 2.97 times higher among people with an LDL level of 115-120, than among people with an LDL level of 80-90, in a study published in 2019 in the Journal of the American Heart Association.
The study examined the risk of cardiovascular disease and all-cause mortality among 3,875 participants, using data collected over an eight-year period.
“Adverse outcomes” were defined as “fatal and non‐fatal atherosclerotic cardiovascular disease (coronary heart disease, stroke, or transient ischemic attack, and intermittent claudication) and death from all causes.”
Most healthy people with LDL above 130 mg/dL had artery clogging by their mid-40s, in one study
Eleven researchers found, in a study of 1,779 middle-aged people without risk factors for cardiovascular disease, that half of had plaque in their arteries, in a study published in 2017 in the Journal of the American College of Cardiology.
The men and women in the study, nearly all in their 40s, each had an LDL level lower than 160, and none of the major risk factors of smoking, family history, high blood pressure or diabetes.
Of these otherwise healthy subjects, 30% had plaque in their arteries supplying blood to the legs, 23% had plaque in their carotid arteries supplying blood to the brain, 17% had plaque in their abdominal aorta, and 11% had calcified plaque in their coronary arteries supplying oxygenated blood to the heart. (The abdominal aorta is the final section of the aorta, the body’s largest artery.)
Researchers tested the first three locations using ultrasound, and the last using a coronary artery calcium test. They found that 23% had plaque in one location, 21% had plaque in two or three locations, and 6% had plaque in four or more locations.
While this study evaluated subjects with no major risk factors, the researchers also noted a previous study they had conducted showing that in a group of middle-aged men and women at “low” risk of cardiovascular disease, 60% had arterial plaque in at least one location, and 41% had plaque in two or more locations.
An editorial comment on the study suggests that arterial imaging at an early stage could be used to guide treatment decisions that could help prevent cardiovascular disease. The study did not include participants with LDL levels above 160 mg/dL, but a study discussed early in this chapter found that for every 30 mg/dL increase in the LDL level, the risk for coronary heart disease increases by about 30%.