Table 2.

Association Between LDL Subfractions and Incident CVD and Severity of CVD

Author, Year (Reference)	Cardiovascular Outcome	Participants	Predictor	Mean Value		P Value	Other Results	P Value	Adjusted for Lipids?	Quality
				Persons With Event	Persons Without Event
Incident CVD
Cromwell et al, 2007 (13)	Incident CVD	1440 men	LDL particle number	1641 nmol/L	1509 nmol/L	<0.001	HR, 1.24 (95% CI, 1.10–1.39) per 1-SD increase in LDL particle number*	<0.001	No	Fair
		1626 women		1628	1344	<0.001	HR, 1.33 (95% CI, 1.17–1.50) per 1-SD increase in LDL particle number*	<0.001	No
							Event-free survival was higher in participants with low LDL particle number, after dichotomization by LDL cholesterol level		Yes
El Harchaoui et al, 2007 (14)	Fatal or nonfatal CAD	1003 case patients, 1885 control participants	Large (212–230 Å) Medium (no data on size) Small (180–212 Å) LDL particle number LDL particle size	43 nmol/L 568 nmol/L 999 nmol/L 1640 nmol/L 210 Å	36 nmol/L 572 nmol/L 885 nmol/L 1525 nmol/L 211 Å	0.003 NS <0.001 <0.001 0.002	OR, 1.37 (95% CI, 1.04–1.83)† OR, 0.86 (95% CI, 0.65–1.15)‡	0.02 NS	No No No Yes No	Good
Otvos et al, 2006 (15)	Nonfatal MI or cardiac death	364 case patients, 697 control participants	Large (212–230 Å)				OR, 1.08 (95% CI, 0.95–1.23) per 1-SD increase§	NS	Yes∥	Fair
			Small (180–212 Å)				OR, 1.11 (95% CI, 0.98–1.27) per 1-SD increase§	NS	Yes∥
			LDL particle number				OR, 1.20 (95% CI, 1.05–1.37) per 1-SD increase§	<0.05	Yes∥
			LDL particle size				OR, 0.97 (95% CI, 0.85–1.10) per 1-SD increase§	NS	Yes∥
Kuller et al, 2002 (16)	Incident MI or angina	Men: 243 case patients, 67 control participants	Large (213–230 Å) Medium (198–212 Å) Small (183–197 Å) LDL particle number LDL particle size	57.3 mg/dL cholesterol 36 mg/dL cholesterol 25.7 mg/dL cholesterol 1676 nmol/L 209 Å	58 mg/dL cholesterol 34.5 mg/dL cholesterol 22.7 mg/dL cholesterol 1597 nmol/L 210 Å	NS NS NS NS NS			No No No No No	Fair
		Women: 191 case patients, 182 control participants	Large (213–230 Å) Medium (198–212 Å) Small (183–197 Å) LDL particle number LDL particle size	96 mg/dL cholesterol 8.2 mg/dL cholesterol 7.1 mg/dL cholesterol 1680 nmol/L 213 Å	104 mg/dL cholesterol 6.8 mg/dL cholesterol 0 mg/dL cholesterol 1501 nmol/L 216 Å	NS NS <0.05 <0.05 <0.05	OR, 1.77 (95% CI, 1.12–2.30), presence vs. absence of subfraction OR, 1.11 (95% CI, 1.03–1.09) per 100nmol/L increase¶ OR, 0.68 (95% CI, 0.51–0.91), unit of comparison not reported	<0.05 <0.05 <0.05	No No Unclear Yes Unclear
Kuller et al, 2007 (17)	Cardiac death	214 case patients, 214 control participants	Large (213–230 Å) Small (182–197 Å) LDL particle size	500.7 nmol/L 1207.1 nmol/L No data	465.8 nmol/L 1200.2 nmol/L No data	NS NS NS	ORs of quartiles and trend (no data) ORs of quartiles and trend (no data)	NS NS	No No No	Fair
Hsia et al, 2008 (18)
Substudy 1	Incident MI, coronary death	202 case patients, 200 control participants	LDL particle number	1673 nmol/L	1513 nmol/L	<0.001**	OR, 1.40 (95% CI, 1.08–1.83) per 1-SD increase††	0.01	No	Fair
Substudy 2	Incident MI, coronary death	149 case patients, 149 control participants	LDL particle number	1687 nmol/L	1525 nmol/L	<0.001	OR, 1.31 (95% CI, 0.97–1.78) per 1-SD increase	0.08	No	Fair
Blake et al, 2002 (19)	Cardiac death, incident MI, or stroke	130 case patients, 130 control paraticipants	Large (213–227 Å) Medium (198–212 Å) Small (183–197 Å) LDL particle number LDL particle size	886 nmol/L 201 nmol/L 0 1597 nmol/L 215 Å	1001 nmol/L 126 nmol/L 0 1404 nmol/L 218 Å	NS 0.008 NS <0.001 0.046	RR, 2.90 (95% CI, 1.16–7.30)‡‡ RR, 1.20 (95% CI, 0.51–2.82)‡‡	0.02 NS	No No No Yes Yes	Good
Campbell et al, 2007 (20)	Intracerebral hemorrhage	41 case patients, 107 control participants	Large (no data on size) Medium (no data on size) Small (no data on size) LDL particle number LDL particle size	396 nmol/L 473 nmol/L 309 nmol/L 1461 nmol/L 208 Å	252 nmol/L 473 nmol/L 377 nmol/L 1558 nmol/L	0.03 NS NS NS	OR, 1.18 (95% CI, 0.98–1.43) per 100-nmol/L increase§§ OR, 2.15 (95% CI, 0.97–4.78) per 10-Å increase§§ OR, 2.16 (95% CI, 0.97–4.80) per 10-Å increase∥∥ OR, 1.53 (95% CI, 0.55–4.30) per 10-Å increase¶¶	0.08   0.06 NS NS	No No No No No Yes Yes	Fair
Soedamah-Muthu et al., 2003 (21)	Incident CAD	59 case patients, 59 control participants	Large (213–230 Å) Medium (198–212 Å) Small (183–197 Å) LDL particle size	603 nmol/L 120 nmol/L 800 nmol/L 206 Å	688 nmol/L 111 nmol/L 526 nmol/L 210 Å	NS ≤0.01 ≤0.001 ≤0.01	No data*** No data*** No data*** No data***	NS NS NS NS	Yes Yes Yes Yes	Fair
CVD severity
Rosenson et al, 2002 (22)	Change in MLD, mm MLD decrease >0.07 mm/y	241 111	Large (213–230 Å) Small (183–197 Å) Large (213–230 Å) Small (183–197 Å) LDL particle number LDL particle size	– – – – – –	– – – – – –		Spearman correlation, 0.03 Spearman correlation, −0.17††† OR, 0.4 (95% CI, 0.1–1.4) for <84 vs. ≥84 mg/dL OR, 9.1 (95% CI, 2.1–39) for <30 vs. ≥30 mg/dL OR, 1.4 (95% CI, 0.3–6.7) for <1825 vs. ≥1825 nmol/L OR, 0.2 (95% CI, 0.1–0.9) for <200 vs. ≥200 Å	NS <0.01 NS <0.05 NS <0.05	Yes Yes Yes Yes Yes Yes	Fair

CAD coronary artery disease; CVD cardiovascular disease; HDL high-density lipoprotein; HR hazard ratio; LDL low-density lipoprotein; MI myocardial infarction; MLD minimum lumen diameter; NMR nuclear magnetic resonance; NS not statistically significant; OR odds ratio; RR risk ratio; Tg triglyceride.

^*Adjusted for age, systolic and diastolic blood pressure, smoking, and lipid medication use.

^†Adjusted for HDL cholesterol and Tg. Fourth quartile compared with first quartile.

^‡Adjusted for LDL particle number. Fourth quartile compared with first quartile.

^§Adjusted for treatment group, age, hypertension, smoking, body mass index, and diabetes mellitus status.

^∥Adjustment for LDL cholesterol, HDL cholesterol, and Tg did not “appreciably change these relations.”

^¶Adjusted for age, race, and LDL cholesterol.

^**Adjusted for treatment group.

^††Adjusted for treatment group, age, smoking, alcohol use, diabetes, and hypertension.

^‡‡Adjusted for Tg and total cholesterol/HDL cholesterol. Fourth quartile compared with first quartile.

^§§Adjusted for matching factors.

^∥∥Adjusted for total cholesterol level.

^¶¶Adjusted for HDL cholesterol.

^***( Multivariable analysis with all predictors and Tg and HDL particle number.

^†††Adjusted for LDL cholesterol, HDL cholesterol, Tg, and other factors.