Cholesterol is Not a Myth—It is a Well-Established, Causal Risk Factor for Cardiovascular Disease
Elevated cholesterol, particularly LDL cholesterol, has been conclusively demonstrated through decades of epidemiological studies and randomized controlled trials to be a major independent risk factor for coronary artery disease, myocardial infarction, and cardiovascular death. 1
The Evidence Base is Overwhelming
The relationship between cholesterol and cardiovascular disease has been validated through multiple lines of evidence:
Epidemiological studies consistently show a continuous positive relationship between LDL cholesterol and coronary heart disease risk down to at least 3-4 mmol/L, with no threshold below which lower cholesterol is not associated with lower risk. 2 A prolonged difference in total cholesterol of about 1 mmol/L is associated with one-third fewer CHD deaths in middle age. 2
Large-scale randomized controlled trials have proven that lowering LDL cholesterol with statins reduces cardiovascular mortality, morbidity, and cardiovascular events in both high-risk patients and those with moderate risk. 1, 3 The epidemiologically predicted differences in CHD risk were achieved within just a few years of treatment. 2
The American Heart Association, American Diabetes Association, and American Cancer Society jointly recognize elevated cholesterol as having "long been recognized as an important independent risk factor for coronary artery disease." 1
LDL Cholesterol is the Primary Culprit
LDL cholesterol is the primary lipoprotein mediating atherosclerosis and is the main target of cholesterol-lowering therapy. 1
Since LDL cholesterol comprises approximately 70% of total cholesterol and has direct atherogenic effects, a 1 mmol/L reduction in LDL cholesterol is associated with 40-50% lower CHD risk. 2
The National Cholesterol Education Program ATP III guidelines identify LDL as the primary target of cholesterol-lowering therapy, with treatment intensity determined by risk stratification. 1
For patients with diabetes or established coronary heart disease, the LDL cholesterol goal is less than 100 mg/dL, with drug therapy initiated at LDL levels of 100 mg/dL or higher. 1
The Risk Extends Across All Age Groups
Contrary to outdated beliefs, elevated LDL cholesterol increases cardiovascular risk even in elderly individuals aged 70-100 years. 4
In a contemporary cohort study, people aged 70-100 years with elevated LDL cholesterol had the highest absolute risk of myocardial infarction and atherosclerotic cardiovascular disease. 4
Risk of myocardial infarction per 1.0 mmol/L increase in LDL cholesterol was amplified for all age groups, particularly those aged 70-100 years (HR 2.99 for LDL ≥5.0 mmol/L vs <3.0 mmol/L in those aged 80-100). 4
The number needed to treat in 5 years to prevent one cardiovascular event was lowest for individuals aged 70-100 years. 4
The Magnitude of the Problem
In 2001,50.7% of the U.S. population had total cholesterol levels of 200 mg/dL or greater, and 45.8% had LDL cholesterol levels of 130 mg/dL or higher. 1
This is not limited to adults—with rising obesity rates, 10% of children ages 12-19 now have total cholesterol exceeding 200 mg/dL. 1
Despite effective screening and treatment options, less than 50% of individuals who meet criteria for lipid-modifying treatment actually receive it, even among those at highest risk with symptomatic coronary heart disease. 1
Half of those prescribed lipid-lowering drugs stop taking them before 6 months, highlighting the critical need for improved compliance. 1
Treatment is Proven Effective and Safe
Statin therapy reduces cardiovascular mortality and morbidity in patients with very high, high, or moderate risk of cardiovascular disease. 3
The cardiovascular benefits of statins far outweigh non-cardiovascular harms in patients with cardiovascular risk. 3
Early concerns about cognitive dysfunction, memory loss, and increased cancer risk have not been proven, with recent data even suggesting possible protective effects. 3
While statins do slightly increase the incidence of type 2 diabetes in people with metabolic syndrome components, the cardiovascular benefits by far exceed this risk. 3
Common Pitfalls to Avoid
Do not confuse dietary cholesterol with blood cholesterol levels. While dietary cholesterol comes from animal sources, dietary cholesterol content does not significantly influence plasma cholesterol values, which are regulated by genetic and nutritional factors affecting cholesterol absorption or synthesis. 5 The primary dietary culprit is saturated fat, not dietary cholesterol itself. 2
Do not dismiss cholesterol as a risk factor based on outlier publications that contradict the overwhelming consensus. 6 The Bradford Hill criteria for causality are satisfied by the cholesterol hypothesis through consistent epidemiological associations, dose-response relationships, temporal sequence, biological plausibility, experimental evidence from randomized trials, and coherence across multiple study types. 1, 2, 4
The absolute benefit of cholesterol reduction is determined by an individual's overall cardiovascular risk, not just their cholesterol level. 2 Therefore, treatment decisions should prioritize those at highest absolute risk, including those with established cardiovascular disease, diabetes, or multiple risk factors. 1, 7