Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with ‘Normal’ LDL-C Levels
Abstract
:1. Introduction
2. Clinical Relevance of LDL Heterogeneity
3. History of Lipoprotein Heterogeneity and Laboratory Methods
Indirect Approximation of LDL Heterogeneity
4. Evidence for LDL Heterogeneity Association with CHD Risk
4.1. Small, Dense LDL-C Quantitative Level and CHD Risk
4.2. Independence of Small, Dense LDL-C as a Risk Predictor
4.3. Statin Therapy and sdLDL-C CHD Risk
4.4. Small Dense LDL, Not Always a Significant Predictor of CVD Events
4.5. Non-Invasive Imaging and Small, Dense LDL
5. Evidence for Treatment Response
Lipid Medications and LDL Heterogeneity
6. Evidence for Clinical Outcome Response
Small Dense LDL and Interventional CV Outcomes
7. Guidelines and Small, Dense LDL
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Study | Year | Findings |
---|---|---|
Framingham [9] | 1966 | Trig rich Sf20-400 lipoproteins associated with CAD risk |
Lawrence Livermore [6] | 1966 | Trig rich Sf20-100 lipoproteins associated with CAD risk |
NHLBI-II [28] | 1987 | IDL linked to arteriographic progression of CAD |
Boston Area Heart [18] | 1988 | LDL pattern B associated with 3-fold increased CAD risk |
STARS [29] | 1992 | Dense (small) LDL best predictor of arteriographic outcome |
Physician’s Health survey [21] | 1996 | LDL pattern B associated with 3.4-fold increased CAD risk independent of total and HDL cholesterol and apo B |
Stanford 5 City Project [20] | 1996 | LDL size best predictor of CAD risk by conditional logistic regression |
MARS [30] | 1996 | In statin treated subjects with LDL-C < 85 mg/dL, triglyceride-rich lipoproteins were correlated with disease progression |
SCRIP [31] | 1996 | Dense LDL predicts arteriographic benefit in the Stanford Coronary Risk Intervention project. |
Quebec CV Study [19] | 1997 | Small LDL related to CHD risk. |
Statistical adjustment for LDL-C, triglycerides, HDL-C, and apoB had virtually no impact on the relationship of small LDL and CHD risk. | ||
CARE [32] | 2001 | Large LDL size was an independent predictor of CHD events. Identifying patients on the basis of LDL size may not be useful clinically since pravastatin effectively treats risk associated with large LDL. |
Healthy Women Study [33] | 2002 | Small low-density lipoprotein (LDL) was positively associated with coronary artery calcium (p < 0.01), but medium and large LDL were not. |
SCRIP [34] | 2003 | Small low-density lipoprotein III but not low-density lipoprotein cholesterol is related to arteriographic progression |
EAST [35] | 2003 | Arteriographic CAD progression over three years was significantly and independently linked to small, dense LDL particles. |
Healthy Women Study [23] | 2009 | CVD risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of standard lipids or apolipoproteins |
HATS [36] | 2014 | Four laboratory methodologies confirm the association of small, dense LDL with greater coronary atherosclerosis progression and the associations were independent of standard lipid measurements. |
ARIC [25] | 2014 | sdLDL-C was associated with future CHD events even in individuals considered at low CVD risk based on their LDL-C level. |
MESA [26] | 2014 | sdLDL-C significantly associated with CHD risk even in subjects with LDL-C < 100 mg/dL who were normoglycemic |
JUPITERr [37] | 2015 | Baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL-C and atherogenic particles including select subfractions of LDL particles. |
AIM-HIGH [38] | 2016 | Levels of HDL3-C, but not HDL-C, HDL2-C, sdLDL, or LDL-TG, predict CV events in patients with metabolic dyslipidemia. |
Malmo Heart [39] | 2017 | Smaller LDL particles are associated with incident CVD independently of traditional risk-factors, including standard lipids |
Sakai [40] | 2018 | sdLDL-C was the most effective predictor of residual risk of future CHD events in stable older male CAD patients using statins and was independent of LDL-C |
Copenhagen Heart Study [30] | 2020 | Individuals with high sdLDL-C had higher MI and ASCVD risk in 38,322 subjects. |
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Superko, H.; Garrett, B. Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with ‘Normal’ LDL-C Levels. Biomedicines 2022, 10, 829. https://doi.org/10.3390/biomedicines10040829
Superko H, Garrett B. Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with ‘Normal’ LDL-C Levels. Biomedicines. 2022; 10(4):829. https://doi.org/10.3390/biomedicines10040829
Chicago/Turabian StyleSuperko, Harold, and Brenda Garrett. 2022. "Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with ‘Normal’ LDL-C Levels" Biomedicines 10, no. 4: 829. https://doi.org/10.3390/biomedicines10040829