Is high cholesterol the main cause of heart disease?
Yes, high cholesterol is a primary cause, but it's not the only one. A large meta-analysis of over 1 million people found that for every increase in total cholesterol, the risk of dying from cardiovascular disease rises by 27% [3]. That's a clear, linear relationship: higher cholesterol means higher risk. But the story gets more complicated when you look at different types of cholesterol.
What about LDL cholesterol—is that the only bad kind?
LDL cholesterol is the classic villain, but it's not the only one. A 2023 study of over 23,000 statin-treated patients found that even when LDL was well-controlled (below 1.8 mmol/L), those with the highest levels of non-HDL cholesterol (which includes all the bad cholesterol types) still had an 80% higher risk of a heart attack or stroke compared to those with the lowest levels [1]. This means that focusing only on LDL can miss a lot of residual risk. Another study of patients with stable angina found that a high ratio of triglycerides to HDL cholesterol predicted heart attacks and death independently of LDL levels [2]. So, while LDL is important, other lipid particles like remnant cholesterol and triglycerides also matter a great deal.
What is remnant cholesterol, and why does it matter?
Remnant cholesterol is the cholesterol left over after you subtract LDL and HDL from your total. It's found in triglyceride-rich particles, and it's a powerful predictor of heart disease. A 2022 study of nearly 42,000 people found that those with the highest remnant cholesterol levels (≥1.6 mmol/L) had a 23% higher chance of being correctly reclassified as high-risk for a heart attack, compared to using standard risk factors alone [5]. This means remnant cholesterol catches risk that other measures miss. Another review confirmed that high remnant cholesterol is consistently linked to increased risk of ischemic heart disease in both men and women, with levels rising sharply in men in early adulthood and in women around menopause [6]. So, if your doctor only checks your LDL, you might still be at risk if your remnant cholesterol is high.
Can low cholesterol ever be bad?
Surprisingly, yes—in certain situations, very low cholesterol is linked to worse outcomes. A study of over 2,800 heart failure patients found that those with the lowest remnant cholesterol levels had a 44% higher risk of death compared to those with moderate levels [7]. Similarly, a study of over 6,200 patients with valvular heart disease found that for every 1 mmol/L drop in total cholesterol, the risk of death or heart failure hospitalization increased by 19% [8]. This doesn't mean high cholesterol is good; it means that in people with advanced heart disease, very low cholesterol may be a sign of frailty or malnutrition, not health. The relationship is U-shaped: both very high and very low levels can be harmful, depending on the context.
About These Sources
This answer is built on 8 peer-reviewed studies — published from 2021 to 2024, 2 from 2024 or later, 5 in Q1 journals, collectively cited 407 times — selected as the most relevant from 10 studies that passed quality screening, drawn from 81 papers retrieved from a database of over 500 million.
Sources used in this answer
Non-HDL cholesterol and residual risk of cardiovascular events in patients with ischemic heart disease and well-controlled LDL cholesterol: a cohort study
In a cohort of 23,641 statin-treated patients with well-controlled LDL, those with the highest non-HDL cholesterol (≥2.7 mmol/L) had an 80% higher risk of ASCVD events compared to those with the lowest levels (<1.7 mmol/L), showing residual risk beyond LDL.
Triglycerides and low HDL cholesterol predict coronary heart disease risk in patients with stable angina
In 355 patients with stable angina, a high triglyceride/HDL ratio independently predicted a 2.85-fold increased risk of death or non-fatal heart attack, even after adjusting for LDL and treatments.
Serum Cholesterol Levels and Risk of Cardiovascular Death: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies
A meta-analysis of 14 studies with over 1 million participants found that each unit increase in total cholesterol was associated with a 27% higher risk of cardiovascular death, with a linear dose-response relationship.
Polygenic risk of high LDL cholesterol and ischemic heart disease in the general population
In 21,485 individuals from the general population, those in the top 1% of a polygenic risk score for high LDL had an 83% higher odds of ischemic heart disease, comparable to the risk from familial hypercholesterolemia mutations.
Elevated Remnant Cholesterol Reclassifies Risk of Ischemic Heart Disease and Myocardial Infarction
In 41,928 individuals without prior heart disease, those with remnant cholesterol ≥1.6 mmol/L had a 23% net reclassification improvement for myocardial infarction risk, meaning many were correctly moved to a higher risk category.
Remnant Cholesterol: Quantification, Concentrations by Sex and Age, and Risk of Ischemic Heart Disease
A review of observational and genetic studies concluded that higher remnant cholesterol is an important cause of ischemic heart disease in both sexes, with concentrations rising sharply in early adulthood for men and around menopause for women.
Predictive value of remnant cholesterol level for all-cause mortality in heart failure patients
In 2,823 heart failure patients, those in the lowest quartile of remnant cholesterol had a 44% higher risk of all-cause mortality compared to the highest quartile, showing a U-shaped relationship.
Total Cholesterol Levels and Risk of Mortality or Heart Failure Rehospitalization in Patients With Valvular Heart Disease.
In 6,235 patients with valvular heart disease, each 1 mmol/L decrease in total cholesterol was associated with a 19% increased risk of death or heart failure rehospitalization, with an optimal cut-off of 3.53 mmol/L.