# Cholesterol and Heart Disease Death: Insights From a Study of 4.5 Million Veterans This large-scale study of more than 4.4 million U.S. military veterans examined how blood cholesterol levels relate to the risk of dying from coronary heart disease. After carefully accounting for age, existing medical conditions, medication use, and other factors, researchers found that the risk of heart disease death increases steadily and continuously as total cholesterol rises above 180 mg/dL. The long-debated "cholesterol paradox" (where very low cholesterol seemed to increase risk) was explained by reverse causality: older and sicker veterans tended to have low cholesterol because of underlying disease, not because low cholesterol is harmful. These findings strongly support the long-standing "lipid hypothesis" that lower cholesterol levels are better for heart health, even when those low levels are achieved through statin medications. # Cholesterol and Heart Disease Death: Insights From a Study of 4.5 Million Veterans ## Table of Contents - Key Points - Background: The Longstanding Cholesterol Debate - Study Methods: How the Research Was Conducted - Study Participants: A Snapshot at Baseline - Key Findings: The Shape of the Cholesterol–Heart Disease Relationship - Age Matters: Different Patterns in Different Age Groups - Preexisting Heart Disease: Similar Patterns, Higher Overall Risk - Statin Medications and the Cholesterol Connection - Clinical Implications: What This Means for Patients - Study Limitations: What This Study Could Not Prove - Recommendations: Practical Advice for Patients - Frequently Asked Questions - Source Information ## Key Points - Among 4.4 million U.S. veterans, heart disease death risk rose continuously as total cholesterol increased above 180 mg/dL. - After full adjustment, low cholesterol carried no increased heart disease death risk, dissolving the cholesterol paradox. - The apparent danger of low cholesterol was reverse causality: older and sicker veterans had low cholesterol due to disease. - Statin-induced low cholesterol was not harmful; starting statins attenuated the risk linked to high baseline cholesterol. - High cholesterol raised risk in all ages, but the strongest relative risk was in veterans aged 18–45. ## Background: The Longstanding Cholesterol Debate For decades, scientists have debated whether lower blood cholesterol is always better for heart health. The **lipid hypothesis** — the theory that lower blood cholesterol leads to a reduced risk of coronary heart disease (CHD) — has been a cornerstone of cardiovascular prevention. But the picture has been complicated. Reports across different populations have shown varying relationships between cholesterol and death. Some studies described a **linear relationship** (risk rises steadily with cholesterol), while others found what researchers call **U-shaped**, **L-shaped**, or **V-shaped** patterns. These shapes suggest that the lowest cholesterol levels might actually be associated with higher risk — a finding that puzzled scientists and challenged the lipid hypothesis. In the 1980s, before statin drugs were widely used, a famous large screening study of middle-aged men showed a continuous, graded relationship between serum cholesterol and CHD risk that persisted even after adjusting for age, race, income, smoking status, blood pressure, diabetes, and prior heart attacks. More recent data from the **Cholesterol Treatment Trialists' Collaboration** has shown that statin therapy reduces the risk of cardiovascular events even in people with low total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C, the "bad" cholesterol). The idea that low cholesterol might somehow be dangerous has persisted, particularly among older individuals and patients with chronic conditions such as heart failure or kidney failure. In these **catabolic conditions** (conditions where the body breaks down more tissue than it builds), cholesterol levels may drop because of the disease itself, chronic inflammation, or malnutrition. This phenomenon is sometimes called **reverse epidemiology** — where a risk factor appears to behave differently in certain patient groups, not because the risk factor is actually protective, but because the underlying disease is driving both the risk factor and the outcome. This debate matters for public health. The U.S. Preventive Services Task Force recently released updated recommendations for statin therapy in primary prevention of cardiovascular disease. Compared with the 2018 American Heart Association/American College of Cardiology guidelines, the newer recommendations reduce eligibility for statin therapy by **15%** among U.S. adults, including **37% fewer patients with diabetes aged 40 to 75 years** who would qualify. Understanding whether the "cholesterol paradox" is real or an artifact of flawed analysis is critical for both clinical practice and public health policy. ## Study Methods: How the Research Was Conducted ### Study Design and Data Source This was a **prospective cohort study** — meaning researchers identified a large group of people, measured their cholesterol levels at the start of the study, and then followed them forward in time to see who developed or died from heart disease. The study used data from the **Veterans Health Administration (VHA)**, which provides medical care for more than 21 million veterans nationwide. The research team extracted electronic health record (EHR) data from the VA Corporate Data Warehouse, identifying veterans who had at least one outpatient lipid panel (cholesterol blood test) between 2002 and 2007. The baseline date for each participant was the date of their first outpatient lipid result during that period. Follow-up continued until December 31, 2018, or until death, whichever came first. ### Exposure: Measuring Cholesterol A panel of clinicians reviewed laboratory values across all VA locations and adjudicated discrepancies to ensure consistent measurements. Only outpatient blood lipid data were used. Because fasting status (whether the patient had eaten before the blood draw) was uncertain, the researchers focused on **total cholesterol (TC)** and **high-density lipoprotein cholesterol (HDL-C, the "good" cholesterol)**, as both are reliable predictors of CHD mortality whether the patient is fasting or not. Participants were divided into **10 total cholesterol groups** (measured in mg/dL): - Less than 120 - 120–139 - 140–159 - 160–179 - 180–199 (used as the reference or "normal" group) - 200–219 - 220–239 - 240–259 - 260–279 - 280 or higher ### Outcome: Defining Heart Disease Death The outcome of interest was **coronary heart disease death**, defined as CHD listed as the primary cause of death. Outcomes were determined using data from the VHA EHR, the Centers for Medicare and Medicaid Services, and the National Death Index. ### Covariates: Accounting for Other Risk Factors The researchers collected detailed information on demographics (age, sex, race) from the EHR. They also identified **13 comorbidities** (chronic diseases diagnosed within 3 years before baseline) using International Classification of Diseases, Ninth Revision (ICD-9) codes: - Hypertension (high blood pressure) - Diabetes - Atrial fibrillation (irregular heart rhythm) - Heart failure - Anemia - Coronary artery disease - Cancer - Stroke - Dementia - Depression - Kidney disease - Liver disease or cirrhosis - Lung disease (chronic obstructive pulmonary disease or asthma) Smoking status (never, former, current, or missing) was determined using EHR data combined with a modified algorithm that generates a probabilistic model of smoking behavior. Body mass index (BMI) was recorded. A national zip code database showing the fraction of adults below U.S. poverty limits was used as a geographic indicator of low-income status. Statin use was tracked at multiple time points: no usage recorded, initiated before or at baseline, within 2 years of follow-up, or after 2 years of follow-up. ### Statistical Analysis: Building the Models The researchers used **Cox proportional hazards regression**, a standard statistical method for analyzing time-to-event data, to estimate the **hazard ratio (HR)** and 95% confidence interval (CI) for CHD death, with the 180–199 mg/dL cholesterol group serving as the reference category. They built three progressively more comprehensive models: 1. **Model 1:** Adjusted for age (continuous), sex, race, and smoking status. 1. **Model 2:** Additionally adjusted for timing of statin therapy initiation, body mass index, baseline hypertension, and baseline diabetes. 1. **Model 3 (the final model):** Further adjusted for HDL-C (continuous) and the presence of 11 chronic diseases. This model also applied a **2-year lag analysis**, meaning deaths occurring within the first 2 years of follow-up were censored (excluded) to reduce the potential for reverse causality — the possibility that undiagnosed disease at the start of the study was lowering cholesterol levels and also increasing death risk. To flexibly model the dose–response relationship, the team used **restricted cubic spline regression** with 3 knots (specific points along the cholesterol range where the curve is allowed to flex). Nonlinearity was tested using the likelihood ratio test. Sensitivity analyses included adjusting for income and socioeconomic status, stratifying by the presence of heart disease at baseline, and evaluating LDL-C, non-HDL cholesterol, and triglycerides separately. All analyses used SAS 9.3, with P values ≤0.05 considered statistically significant. ## Study Participants: A Snapshot at Baseline A total of **4,467,942 adult veterans** nationwide had a complete lipid profile at baseline and were included in the study. This is one of the largest studies of cholesterol and heart disease death ever conducted. The distribution of total cholesterol levels was: - **9.6%** had very low TC (≤140 mg/dL) - **33.0%** had low TC (140–179 mg/dL) - **19.6%** had normal TC (180–199 mg/dL) - **26.2%** had high TC (200–239 mg/dL) - **11.6%** had very high TC (≥240 mg/dL) Some striking patterns emerged in baseline characteristics. Veterans in the **lowest cholesterol group** (TC <120 mg/dL) tended to have the **lowest HDL-C levels** (average 38.2 mg/dL compared with 57.1 mg/dL in the highest TC group), the **greatest average age** (66.1 years vs. 58.6 years), a **higher likelihood of having started statin therapy before baseline** (42.0% vs. 24.0% for the <120 mg/dL group), and the **highest prevalence of nearly every comorbidity** measured. This baseline profile is the first clue to the "cholesterol paradox." The veterans with the lowest cholesterol were, on average, older and sicker than those with higher cholesterol. They had more hypertension, diabetes, coronary artery disease, heart failure, cancer, kidney disease, and lung disease. This is exactly the pattern expected if **reverse causality** were at work: serious illness lowers cholesterol, rather than low cholesterol causing harm. Medication patterns also differed by cholesterol group. More than one-third of veterans with low or very low TC (34.9% and 38.3%, respectively) had initiated statin therapy before or at baseline, while more than 40% of veterans with very high TC (≥280 mg/dL) started statin therapy within the first 2 years of follow-up. This reflects appropriate clinical practice — treating high cholesterol with medication — but it also means that a person's cholesterol group at baseline doesn't necessarily reflect their lifetime exposure. ## Key Findings: The Shape of the Cholesterol–Heart Disease Relationship The relationship between total cholesterol and the risk of dying from heart disease changed depending on how thoroughly the researchers adjusted for other factors. This progression is itself a major finding. **Model 1** (adjusting only for age, sex, race, and smoking) produced a **V-shaped** relationship, with the lowest risk of CHD death at a TC of about 207 mg/dL. Both lower and higher cholesterol appeared to carry increased risk. **Model 2** (adding adjustments for BMI, statin use, diabetes, and hypertension) produced a **U-shaped** relationship, with the lowest risk at TC levels of 200 to 215 mg/dL, and elevated risk at both the low and high ends of the cholesterol spectrum. **Model 3** (the comprehensive model with the 2-year lag analysis and adjustments for HDL-C and 11 chronic diseases) produced a **J-shaped** relationship that tells a much clearer story: the risk of CHD death was **flat for TC below 180 mg/dL** — meaning low cholesterol was not associated with any increased risk — and then increased continuously, in a graded fashion, as cholesterol rose above 180 mg/dL. Compared with veterans whose TC was 180–199 mg/dL (the reference group), the fully adjusted hazard ratios for CHD death were: - TC 200–219 mg/dL: **1.03** (95% CI, 1.02–1.04) — a 3% higher risk - TC 220–239 mg/dL: **1.07** (95% CI, 1.06–1.09) — a 7% higher risk - TC 240–259 mg/dL: **1.15** (95% CI, 1.13–1.18) — a 15% higher risk - TC 260–279 mg/dL: **1.25** (95% CI, 1.22–1.28) — a 25% higher risk - TC ≥280 mg/dL: **1.45** (95% CI, 1.42–1.49) — a 45% higher risk These hazard ratios mean, for example, that a veteran with a total cholesterol of 280 mg/dL or higher was **45% more likely** to die from coronary heart disease during the follow-up period than a similar veteran with cholesterol in the 180–199 mg/dL range, after accounting for all other measured risk factors. The results were **consistent between men and women** (P for interaction between TC and sex = 0.41), meaning the pattern held true across genders. Adjusting for income and socioeconomic status in sensitivity analyses did not materially change the results. ## Age Matters: Different Patterns in Different Age Groups One of the most important contributions of this study is its detailed analysis of how age influences the cholesterol–heart disease relationship. The researchers divided veterans into three age groups and found strikingly different patterns: - **Ages 18–45 years:** J-J-J-shaped pattern - **Ages 45–64 years:** V-U-J-shaped pattern - **Ages 65 years and older:** L-U-J-shaped pattern Statistical testing confirmed that age significantly modified the relationship between cholesterol and heart disease death (**P for interaction between TC and age group <0.001**), meaning the effect of cholesterol on CHD death genuinely differs across age groups. Comparing veterans with normal TC (180–199 mg/dL) to those with higher levels, the hazard ratios for CHD death were: **Younger veterans (ages 18–45):** - TC 200–219: 1.03 (95% CI, 0.92–1.15) - TC 220–239: 1.17 (95% CI, 1.04–1.32) - TC 240–259: 1.40 (95% CI, 1.23–1.59) - TC 260–279: 1.32 (95% CI, 1.13–1.55) - TC ≥280: 1.96 (95% CI, 1.71–2.24) Younger veterans with very high cholesterol (≥280 mg/dL) had nearly **double the risk** of dying from heart disease compared with those in the normal range. **Middle-aged veterans (ages 45–64):** - TC 200–219: 1.02 (95% CI, 1.00–1.05) - TC 220–239: 1.08 (95% CI, 1.05–1.11) - TC 240–259: 1.17 (95% CI, 1.14–1.21) - TC 260–279: 1.25 (95% CI, 1.20–1.29) - TC ≥280: 1.41 (95% CI, 1.36–1.46) **Older veterans (ages 65 and above):** - TC 200–219: 1.03 (95% CI, 1.01–1.04) - TC 220–239: 1.06 (95% CI, 1.04–1.08) - TC 240–259: 1.12 (95% CI, 1.09–1.14) - TC 260–279: 1.21 (95% CI, 1.18–1.25) - TC ≥280: 1.34 (95% CI, 1.29–1.99) The pattern was consistent: the risk of dying from CHD rises progressively with higher cholesterol levels in every age group. However, the magnitude of the effect was most dramatic in **younger veterans**. This may reflect the fact that younger individuals with very high cholesterol have a more severe genetic or lifelong cholesterol burden, while in older adults, competing health risks and the cholesterol-lowering effects of chronic disease weaken the observed association. The reversal of the apparent "danger" of low cholesterol in the older group after full adjustment — where the L-shaped curve transformed into a J-shaped curve — supports the researchers' conclusion that **reverse causality, especially among older participants, accounted for the high risk of CHD death seen in those with low cholesterol levels.** ## Preexisting Heart Disease: Similar Patterns, Higher Overall Risk The researchers also examined whether having heart disease at baseline changed the relationship. They stratified the analysis into veterans with heart disease (atrial fibrillation, heart failure, or coronary artery disease diagnosed before baseline) and those without. Among veterans **with heart disease** at baseline, compared with those with normal TC (180–199 mg/dL), the hazard ratios for CHD death were: - TC 200–219: 1.02 (95% CI, 1.00–1.03) - TC 220–239: 1.06 (95% CI, 1.04–1.08) - TC 240–259: 1.13 (95% CI, 1.10–1.16) - TC 260–279: 1.23 (95% CI, 1.19–1.28) - TC ≥280: 1.42 (95% CI, 1.37–1.47) Among veterans **without heart disease** at baseline, the corresponding hazard ratios were: - TC 200–219: 1.04 (95% CI, 1.02–1.06) - TC 220–239: 1.10 (95% CI, 1.08–1.13) - TC 240–259: 1.20 (95% CI, 1.17–1.23) - TC 260–279: 1.30 (95% CI, 1.26–1.34) - TC ≥280: 1.54 (95% CI, 1.49–1.60) Both groups showed the same J-shaped pattern — flat risk at low cholesterol, rising risk at higher cholesterol — but the effect of high cholesterol was **more pronounced in veterans without preexisting heart disease** (P for interaction <0.001). This makes sense: in people who already have heart disease, the disease itself is the dominant driver of mortality, somewhat diluting the relative contribution of cholesterol levels. ## Statin Medications and the Cholesterol Connection A critical question for patients is whether cholesterol-lowering medication changes the story. The researchers stratified the analysis by statin use and found that the J-shaped pattern held across all groups, but with important nuances. **Veterans who did not use statins** and **veterans who used statins at or before baseline** both showed similar J-shaped relationships between TC and CHD death. Among veterans not using statins, the hazard ratio for CHD death with TC ≥280 mg/dL compared with normal TC (180–199 mg/dL) was **1.83 (95% CI, 1.68–1.99)** — nearly double the risk. Among those who had started statin therapy at or before baseline, the hazard ratio for TC ≥280 mg/dL was lower: **1.45 (95% CI, 1.40–1.51)**. A **slight U-shaped relationship** was seen among veterans who started statin therapy after baseline. Higher baseline TC was associated with higher CHD mortality risk, but the effect was **attenuated** (weakened) among veterans who initiated statins during follow-up. This suggests that starting statin therapy reduced the risk associated with high cholesterol. These findings are reassuring and clinically important: **the lipid hypothesis held true even when low cholesterol was achieved through statin medication.** In other words, low cholesterol caused by statins is not harmful — it is associated with reduced, not increased, heart disease death risk. The idea that statin-induced low cholesterol might somehow be dangerous was not supported by this study. ## Clinical Implications: What This Means for Patients This study provides strong, large-scale evidence supporting the lipid hypothesis: **lower blood cholesterol is associated with reduced coronary heart disease risk, and higher cholesterol is associated with increased risk in a continuous, graded fashion.** For patients, several key messages emerge: - **The "cholesterol paradox" appears to be a statistical illusion.** When studies fail to adequately adjust for underlying illness, age, and other confounders, low cholesterol can appear harmful. This study shows that after rigorous adjustment, low cholesterol carries no excess heart disease death risk. - **Reverse causality explains the apparent danger of low cholesterol.** Older and sicker patients tend to have lower cholesterol because of their diseases, not because low cholesterol is harmful. The diseases themselves — heart failure, cancer, kidney disease, chronic inflammation — drive both the low cholesterol and the higher death rate. - **Higher cholesterol gradationally increases risk.** There is no threshold effect. Risk rises steadily from 180 mg/dL upward, reinforcing the importance of keeping cholesterol in a healthy range. - **Statin therapy is not something to fear regarding low cholesterol.** Patients whose cholesterol is lowered with statins or other lipid-lowering medications do not face a paradoxical increase in risk. The benefit of lowering cholesterol was confirmed across all statin-use groups. - **Age is an important modifier.** The relative risk associated with high cholesterol was strongest in younger veterans (ages 18–45), where TC ≥280 mg/dL was associated with nearly double the risk of CHD death. This underscores the importance of addressing high cholesterol early in life. The authors state plainly: **"Clinical practice based on the lipid hypothesis should not be challenged."** For doctors and patients alike, this means the foundational principle of cholesterol management — that lowering cholesterol reduces heart disease risk — remains firmly supported by evidence. ## Study Limitations: What This Study Could Not Prove While this is one of the largest and most comprehensive studies of its kind, it has limitations that should be acknowledged: - **Observational design:** Because this is an observational cohort study (not a randomized controlled trial), it can demonstrate associations but cannot prove causation. The researchers used extensive statistical adjustments to reduce confounding, but unmeasured factors could still influence results. - **Single lipid measurement:** Baseline cholesterol was based on a single outpatient lipid panel. Cholesterol levels can change over time, and the study did not capture long-term cholesterol trajectories for most analyses. - **Veteran population:** The study population was predominantly male (about 93% men) and consisted entirely of veterans using VHA services. Results may not fully generalize to women, non-veterans, or populations with different demographic characteristics. - **Uncertain fasting status:** Because fasting status was uncertain, the primary analysis focused on total cholesterol and HDL-C. Triglycerides, LDL-C, and non-HDL cholesterol were analyzed only in sensitivity analyses. - **Reverse causality can never be fully excluded:** Even with the 2-year lag analysis and comprehensive adjustments, the possibility remains that some unmeasured disease process at baseline influenced both cholesterol levels and mortality risk. - **CHD death as the sole outcome:** The study examined death from coronary heart disease specifically. The relationship between cholesterol and other outcomes (such as nonfatal heart attacks, strokes, or total mortality) was not the focus of this analysis. ## Recommendations: Practical Advice for Patients Based on this research and the broader body of scientific evidence, here are actionable recommendations: 1. **Know your cholesterol numbers.** Talk to your doctor about getting a lipid panel (blood test) that measures total cholesterol, HDL-C, LDL-C, and triglycerides. This study used total cholesterol as the primary measure, but your doctor will consider all fractions to assess your risk. 1. **Don't fear low cholesterol.** If your cholesterol is low — especially if it's low because you're taking a statin — there is no evidence from this study that this puts you at higher risk of dying from heart disease. The opposite is true. 1. **If you are young, pay special attention to high cholesterol.** This study found the strongest relative risk associated with very high cholesterol (≥280 mg/dL) among veterans aged 18–45 years. Early intervention to control cholesterol may yield the greatest lifelong benefit. 1. **Take statins as prescribed.** If your doctor has recommended statin therapy, this study provides reassurance that lipid-lowering treatment is safe and effective. Veterans who started statins during follow-up had attenuated risk compared with those who did not. 1. **Focus on overall cardiovascular health.** Cholesterol is one important risk factor, but it does not act alone. Blood pressure control, diabetes management, smoking cessation, healthy weight, and regular physical activity all contribute to reducing heart disease risk. 1. **Ask your doctor about your individual risk.** Official guidelines have changed over time regarding who should take statins for primary prevention. Discuss your personal risk profile — including age, cholesterol levels, blood pressure, diabetes status, and family history — with your healthcare provider to make an informed decision. ## Frequently Asked Questions ### What is the cholesterol paradox, and is it a real danger? The cholesterol paradox is the idea that very low cholesterol increases heart disease death risk. In an analysis of 4.4 million U.S. veterans, this appeared only before adjusting for age and illness. After thorough adjustment, low cholesterol carried no increased risk. The apparent danger was explained by reverse causality: older, sicker patients had low cholesterol because of disease. ### Should I worry if my total cholesterol is low? No. In this large veterans study, after accounting for age, chronic diseases, and other factors, low total cholesterol was not associated with any increased risk of dying from coronary heart disease. The higher risk seen in unadjusted analyses was due to underlying illness, not the low cholesterol itself. Low cholesterol from statin use was also not harmful. ### What does this research say about statins and low cholesterol? It provides reassurance. Among veterans whose low cholesterol was achieved with statin therapy, there was no paradoxical increase in heart disease death risk. Instead, those who started statins during follow-up had a weaker association between high baseline cholesterol and death, suggesting benefit. The study supports the lipid hypothesis that lower cholesterol is better, even when medication achieves it. ### At what total cholesterol level does heart disease death risk start to increase? In fully adjusted analyses, the risk of dying from coronary heart disease was flat for total cholesterol below 180 mg/dL and then rose continuously and steadily above that level. For example, compared with 180–199 mg/dL, a total cholesterol of 280 or higher was linked to a 45% higher risk of heart disease death. ### Does age change how cholesterol affects heart disease risk? Yes. Age significantly modified the relationship. High cholesterol raised heart disease death risk in every age group, but the relative effect was strongest in younger veterans aged 18–45. In that group, total cholesterol of 280 or higher was linked to nearly double the risk compared with normal cholesterol, emphasizing the importance of addressing high cholesterol early. ### If I already have heart disease, does high cholesterol still matter? Yes, but the relative effect is somewhat smaller. Veterans with existing heart disease showed the same J-shaped pattern: flat risk at low cholesterol and rising risk at higher cholesterol. However, the increased risk from very high cholesterol was more pronounced in those without preexisting heart disease, because the disease itself strongly influences mortality. ### What are the limitations of this cholesterol research? This was an observational study, so it cannot prove causation. Baseline cholesterol was a single measurement, fasting status was uncertain, and the population was mostly male veterans, so results may not fully apply to women or non-veterans. Even with careful adjustments, reverse causality from unmeasured disease can never be completely excluded. ### Should I get a second opinion before starting statins for high cholesterol? A second opinion can help when your doctor recommends statins and your cholesterol is above 180 mg/dL, because research in over 4 million veterans shows heart disease death risk rises continuously as total cholesterol climbs above that level. Conversely, low cholesterol achieved with statins is not dangerous; the apparent 'cholesterol paradox' reflects reverse causality in older, sicker patients. If you are young, very high cholesterol carries the strongest relative risk, so early treatment decisions matter. An independent expert review can clarify whether your treatment plan fits your individual risk. Diagnostic Detectives Network provides independent expert second opinions. ## Source Information **Original Article Title:** nguyen-et-al-2023-serum-cholesterol-and-impact-of-age-on-coronary-heart-disease-death-in-more-than-4-million-veterans **Authors:** Xuan-Mai T. Nguyen, PhD; Yuk-Lam Ho, MPH; Yanping Li, PhD; Rebecca J. Song, PhD; Kenneth H. Leung, MD; Saad Ur Rahman, MBBS; Ariela R. Orkaby, MD, MPH; Jason L. Vassy, MD; David R. Gagnon, MD, PhD; Kelly Cho, PhD; J. Michael Gaziano, MD, MPH; Peter W. F. Wilson, MD **Journal:** Journal of the American Heart Association (JAHA), 2023; Volume 12, Article e030496. DOI: 10.1161/JAHA.123.030496 **Publication Date:** 2023. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivs License. **Funding and Disclosures:** The study was conducted using data from the Veterans Health Administration, with approval from the --- Publisher: Diagnostic Detectives Network (https://diagnosticdetectives.com) — independent multi-expert medical second opinions, worldwide, private-pay. Author byline: Anton Titov, MD, PhD. Contact: https://diagnosticdetectives.com/pages/contact Canonical page: https://diagnosticdetectives.com/products/cholesterol-and-heart-disease-death-insights-from-a-study-of-4-5-million-veterans