LDL cholesterol and cardiovascular disease
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LDL Cholesterol and Cardiovascular Disease Risk
LDL Cholesterol as a Major Cardiovascular Risk Factor
Low-density lipoprotein cholesterol (LDL-C) is widely recognized as a major risk factor for cardiovascular disease (CVD) and is included in most global risk prediction tools and prevention guidelines. Elevated LDL-C levels are linked to a significant worldwide burden of disease, with millions of deaths and disability-adjusted life years attributed to high LDL-C, especially in countries with lower socio-demographic indices .
Long-Term and Cumulative LDL-C Exposure
Research shows that both the level and duration of LDL-C exposure are important. Higher cumulative LDL-C exposure from young adulthood through middle age increases the risk of coronary heart disease (CHD) later in life, independent of LDL-C levels measured only in midlife Domanski2020Zhang2021. The risk is greater when high LDL-C exposure occurs earlier in life, emphasizing the importance of early and sustained LDL-C control .
LDL-C and Cardiovascular Mortality in Low-Risk and Older Populations
Even among individuals considered at low 10-year risk for atherosclerotic CVD, higher LDL-C levels (≥160 mg/dL) are associated with a 50% to 80% increased risk of CVD mortality over the long term . In older adults (ages 70–100), elevated LDL-C is strongly linked to higher absolute risks of myocardial infarction and atherosclerotic CVD, with the greatest benefit from LDL-C lowering seen in this age group .
Predictive Value of LDL-C by Age and Disease Status
LDL-C is a stronger predictor of premature CHD and ASCVD death in middle-aged adults, but its association with CVD outcomes weakens with age, especially for stroke . However, in people with evidence of coronary atherosclerosis (as shown by coronary artery calcification), LDL-C is closely associated with future ASCVD events, while in those without such evidence, the association is much weaker .
Achieving and Maintaining Low LDL-C Levels
Lowering LDL-C to very low levels (even below 20 mg/dL) in patients with established atherosclerotic CVD is associated with a reduced risk of cardiovascular events, with no significant increase in safety concerns over long-term follow-up . Despite guideline recommendations, more than half of patients with ASCVD in real-world settings have uncontrolled LDL-C (≥70 mg/dL), with notable disparities by sex and race, and most are not started on lipid-lowering therapy after an elevated LDL-C result .
LDL-C Measurement and Early Risk Stratification
Accurate assessment of LDL-C in childhood is important for predicting long-term cardiovascular risk. The Sampson equation has been shown to provide the most accurate estimation of elevated childhood LDL-C and better predicts adult cardiovascular events compared to other commonly used equations .
Conclusion
LDL cholesterol is a key modifiable risk factor for cardiovascular disease across all ages. Both the level and duration of LDL-C exposure matter, with early and sustained control offering the greatest benefit. Lowering LDL-C, even to very low levels, is safe and effective in reducing cardiovascular events, especially in those with established atherosclerosis or at higher absolute risk. However, significant gaps remain in real-world LDL-C management, highlighting the need for improved and equitable care strategies. Early and accurate assessment, along with prompt intervention, can help reduce the global burden of cardiovascular disease linked to LDL cholesterol.
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