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Is LDL particle size important?  

Studies indicate that individuals with greater distribution of small and dense LDL particles have much higher risk for developing CHD.   

Currently, the level of LDL-C is calculated through the measurement of triglyerides and HDL-C, all of which are accepted to be strongly predictive of CHD.  

Atherogenic particles, like LDL-P, ApoB, Lp(a), and small dense LDL have gained the interest of researchers and clinicians in the last decade,

and the evidence highlighting their predictive strength over LDL-C in assessing risk has been elucidated. Unlike LDL-C, LDL-P is an actual measure of LDL particles.  Numerous studies indicate that LDL-P may be a stronger predictor of CHD than LDL-C. The 2018 Guideline on the Management of Blood Cholesterol included a new section, ASCVD Risk Enhancers, that included apoB and Lp(a), which may be used with borderline or intermediate risk individuals to further refine the primary prevention management of these individuals.

Small dense LDL has not been included in the guidelines, but the evidence is growing.  In numerous studies, sdLDL provided incremental clinical value beyond the traditional lipid profile.  Numerous studies, including the MESA (Multi-ethnic study of atherosclerosis), highlighted the predictive strength of elevated sdLDL. In the top quartile (HR 2.37) sdLDL identified individuals that were 2x more likely to develop CHD than the first quartile in the low LDL-C group. Importantly, elevated LDL-C, compared to those in the optimal group, exhibited no significant risk.

In the ARIC (Atherosclerosis risk in communities) cohort, consisting of 11,419 men and women, in a risk-categorized analyses, where LDL <100mg/dL and quartile four for sdLDL, sdLDL was predictive of CHD at 61% increase risk.  In the same analysis, when LDL was >100 mg/dL and sdLDL was elevated, individuals were at the highest risk of developing CHD.

Recently, a prospective study involving 38,322 individuals from the Denmark, Copenhagen General Population Study, showed that higher levels of sdLDL predicted MI and ASCVD. The multivariate analysis highlighted the strength of sdLDL in providing risk profiles that properly reclassifies individuals that may have been identified as low to moderate risk.

 

When sdLDL is combined with traditional lipid profiles and clinical evaluations, hidden risks for CHD are revealed. As a clinician, this enables you to deploy therapy and care that improves health outcomes.

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sdLDL-C predicted risk for incident CHD even in individuals who would be considered at low cardiovascular risk based on their LDL-C level

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Clinically, sdLDL-C assessment may be most beneficial in patients with intermediate CHD risk, where those with higher sdLDL-C levels may be designated for more aggressive treatment protocols.

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  1. Tsai, MY, et al.  New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: the Multi-ethnic Study of Atherosclerosis.  Arterioscler Thromb Vasc Biol. 2014;34(1):196-201.  doi:10.1161/ATVBAHA.113.302401.

  2. Hoogeveen, RC, et al.  Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.  Arterioscler Thromb Vasc Biol. 2014;34(5):1069-`077. doc:10.1161/ATVBAHA.114.303284

  3. Balling, M, et al.  Small dense Low-density Lipoprotein Predicts Atherosclerotic Cardiovascular Disease in the Copenhagen General Population Study.  J Am Coll Cardiol. 2020 Jun, 75 (22), 2873-2875.

Helping to Enhance Risk Assessment for ASCVD