Guidelines and medication scale

• As a risk factor for heart disease, cholesterol has much less importance; the key question is not whether high LDL is a risk factor, but how important that risk is.
• The 2026 American Heart Association lipid guidelines call for screening children at ages 9–11, screening every five years by age 20, LDL targets around 55–70 mg/dL, and aggressive drug therapy when LDL is high without waiting and watching, while the evidence points the other way. [1]
• Applying the new guidelines would medicate about 56.5% of adults aged 30–79, about 85% at ages 60–69, about 93% by age 70, and add more than 21 million people to cholesterol medication. [2]
• That scale gives cholesterol a dominant role even though several other cardiovascular risks are much larger.

PREVENT and risk magnitude

• The AHA PREVENT calculator was built from more than 6 million patients in 45 studies and compares diabetes, high blood pressure, smoking, kidney disease, lipids, and other cardiovascular risk factors. [3]
• PREVENT uses non-HDL: triglycerides and HDL are separate from LDL, high carbohydrate intake raises triglycerides and lowers HDL, and non-HDL brings triglyceride-related risk into the measure even though statins and similar drugs mainly target LDL. [3]
• A hazard ratio of 1.0 is neutral and 2.0 means double the risk, so the magnitude of a risk factor is the relevant distinction.
• In PREVENT, diabetes raises cardiovascular risk about 60–65%, smoking about 60%, high blood pressure about 36%, kidney disease is important, and higher HDL is protective; non-HDL has a hazard ratio of 1.0 in women and only about a 5% increase in men. [3]
• Smoking or diabetes is roughly 10–12 times more important than LDL cholesterol; because the 5% figure comes from non-HDL, which also includes triglycerides, LDL itself has even less importance.
• A focus on medicating more than 90% of older Americans for LDL gives less attention to diabetes, smoking, and blood pressure, which carry much larger risks.

Statin use and the Women's Health Study

• A BMJ study of national statin use shows North America using far more statins than other regions and increasing faster; in 2020 about 26.1% of the population used a statin compared with 20% or less elsewhere. [4]
• Greater focus on diabetes and diet, including cutting carbohydrates to lower blood sugar, addresses larger risks, while doctors spend almost no time on diet and extensive time on cholesterol.
• The U.S. uses far more statins than Japan, yet Japan has very high life expectancy and very low heart-disease rates; cholesterol does not explain the whole difference, but statins are not that important.
• In the Women's Health Study analysis in JAMA Cardiology, women under 55 with diabetes had a hazard ratio of about 10.7 for heart disease, compared with 1.38 for LDL cholesterol; the LDL increase is still meaningful, but diabetes and metabolic syndrome carry much larger risks. [5]
• Diet and diabetes warrant about ten times more attention than cholesterol; diet takes clinical time, more patients generate more payment, and writing a statin prescription takes seconds.

Large global cohorts

• A New England Journal of Medicine analysis included about 1.5 million people from 34 countries and 112 studies, with an average age of 54.4 years and average follow-up of 7.4 years, and estimated the effect of modifying five major risk factors. [6]
• Eliminating diabetes or stopping smoking substantially lowers cardiovascular risk and total mortality, while lowering cholesterol has a much smaller cardiovascular effect and no effect on total mortality; statin-mediated cholesterol lowering therefore does not change the risk of dying in these data. [6]
• Heart disease may decrease, but if total mortality does not fall, other non-cardiac deaths must increase enough to offset the difference; total mortality is the crucial outcome. [6]
• A 2025 New England Journal of Medicine analysis of about 2 million people from 133 cohorts estimates that not smoking adds about 4.8–5.5 cardiovascular-disease-free years and not having diabetes adds about 4.2–4.7, while low cholesterol after medication is associated with losing about 0.4–1.3 years. [7]
• For all-cause survival, not having diabetes adds about 5.8–6.5 years, while low cholesterol after medication is associated with losing about 0.9–1.3 years; around ages 55–60, modifying hyperlipidemia adds only about 0–0.1 cardiovascular-disease-free years and loses about 0.2–0.3 years of overall life. [7]
• Cholesterol can still be lowered in some situations, but high blood pressure, diabetes, and smoking are much more important areas of focus.

Low LDL, mortality, and dialysis

• Sufficiently low cholesterol does not make heart disease impossible merely because plaque contains cholesterol and babies have low cholesterol; adults should not be compared with babies.
• In the Danish study, the LDL level associated with the lowest all-cause mortality was about 140 mg/dL, LDL below about 55 mg/dL was associated with roughly 50% higher mortality, and the lowest mortality clustered around the 60th–95th percentile and not at low LDL. [8]
• As LDL approaches very low levels, mortality rises; some very low LDL occurs with malnutrition and other illness, so very low LDL does not make heart disease impossible.
• Dialysis patients often have LDL around 68–81 mg/dL while still having extensive heart disease.
• Their estimated heart-disease risk is roughly 10–20 times higher than in the general population, so very low LDL does not eliminate cardiovascular disease.
• Dialysis patients still receive cholesterol-lowering medication despite those very low LDL levels and very high cardiovascular risk.

Stopping statins and priorities

• In a recent Lancet Healthy Longevity unblinded randomized trial of adults aged 75 years or older, stopping statins was compared with continuing them, and stopping did not increase heart disease or death. [9]
• Diabetes, smoking, and high blood pressure greatly increase heart-disease risk, and reducing those risks lowers heart disease; LDL has only a tiny effect and may even be harmful.
• The U.S. has the most aggressive LDL targets anywhere; no other country sees this as necessary, yet the AHA keeps pushing levels lower even though lower levels are associated with higher mortality.
• Lupus can carry about a 50-fold higher heart-disease risk, and the excess risk comes from inflammation, not cholesterol. [10]
• Rheumatoid arthritis carries about 1.5-times higher mortality.
• The main priorities are stopping smoking, eliminating diabetes through diet, and monitoring and controlling high blood pressure; cholesterol has much less importance.
• Statins are relatively safe but still have side effects and costs, so their use depends on the magnitude of cholesterol risk and the larger risks that can be changed.

References

1. [00:24] 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia — https://doi.org/10.1161/CIR.0000000000001423
2. [01:25] Implications of the 2026 Dyslipidemia Guideline for Primary Prevention Statin Therapy — https://doi.org/10.1001/jama.2026.11246
3. [02:50] Development and Validation of the American Heart Association's PREVENT Equations — https://doi.org/10.1161/CIRCULATIONAHA.123.067626
4. [07:24] Global, regional and national trends in statin utilisation in high-income and low/middle-income countries, 2015–2020 — https://doi.org/10.1136/bmjopen-2022-061350
5. [09:14] Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women — https://doi.org/10.1001/jamacardio.2020.7073
6. [11:01] Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality — https://doi.org/10.1056/NEJMoa2206916
7. [12:46] Global Effect of Cardiovascular Risk Factors on Lifetime Estimates — https://doi.org/10.1056/NEJMoa2415879
8. [16:10] Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study — https://doi.org/10.1136/bmj.m4266
9. [18:11] Discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older (SAGA/SITE): a multicentre, open-label, pragmatic, non-inferiority randomised trial — https://doi.org/10.1016/j.lanhl.2026.100884
10. [19:28] Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study — https://doi.org/10.1093/oxfordjournals.aje.a009122