Table 1.

Relevant clinical investigations that have contributed to understanding the role of small, dense LDL in cardiovascular risk ranked by date of publication.

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.

STARS = Saint Thomas Arteriographic Regression Trial; HATS = HDL Atherosclerosis Treatment Study; ARIC = Atherosclerosis Risk in Communities; MESA = Multi Ethnic Study of Atherosclerosis; JUPITER = Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin; EAST = Emory Angioplasty and Surgery Trial; SCRIP = Stanford Coronary Risk Intervention Project; AIM-HIGH = Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial.