Complementary prediction of cardiovascular events by estimated apo- and lipoprotein concentrations in the working age population. The Health 2000 Study

Figures & data

Figure 1. Correlation of (A) apoA-I, (B) apoB, and (C) apoB/apoA-I extended Friedewald estimates with actual measured concentrations. The dashed lines represent regression lines. Bland–Altman plots for the cross-validation of measured and extended Friedewald estimates of (D) apoA-I, (E) apoB, and (F) apoB/apoA-I. Bias was determined as difference between estimated and measured values. The dashed lines represent regression lines. The solid lines represent mean bias ± SD. The dashed line represents the mean bias and the solid lines represent ± 2 SD.

Table I. Characteristics of the measured and estimated serum lipoprotein and apolipoprotein concentrations in the cohort. Data are presented as mean (SD). FW refers to the Friedewald formula (1) and EFW to the extended Friedewald approach (19).

	All	Men	Women	P value
Serum/FW-estimated (mmol/L)
TG	1.57 (1.09)	1.84 (1.34)	1.34 (0.71)	< 0.0001
TC	5.90 (1.11)	5.99 (1.12)	5.81 (1.09)	< 0.0001
HDL-C	1.34 (0.38)	1.21 (0.34)	1.46 (0.38)	< 0.0001
LDL-C	3.68 (1.05)	3.85 (1.06)	3.53 (1.02)	< 0.0001
LDL-C/HDL-C	3.00 (1.32)	3.44 (1.41)	2.61 (1.09)	< 0.0001
TC/HDL-C	4.76 (1.70)	5.33 (1.87)	4.24 (1.33)	< 0.0001
non-HDL-C	4.56 (1.15)	4.78 (1.17)	4.36 (1.10)	< 0.0001
apoA-I (g/L)	1.60 (0.29)	1.52 (0.26)	1.67 (0.30)	< 0.0001
apoB (g/L)	1.21 (0.30)	1.28 (0.30)	1.14 (0.28)	< 0.0001
apoB/apoA-I	0.78 (0.25)	0.87 (0.26)	0.70 (0.21)	< 0.0001
EFW-estimated (mmol/L)
VLDL-TG	0.90 (0.78)	1.09 (0.94)	0.72 (0.54)	< 0.0001
IDL-C	0.33 (0.15)	0.36 (1.59)	0.30 (0.14)	< 0.0001
EFW-LDL-C	3.87 (0.89)	3.93 (0.90)	3.84 (0.87)	0.017
HDL2-C	0.85 (0.35)	0.73 (0.30)	0.95 (0.36)	< 0.0001
HDL3-C	0.50 (0.05)	0.49 (0.06)	0.51 (0.05)	< 0.0001
apoA-I (g/L)	1.57 (0.25)	1.50 (0.22)	1.63 (0.25)	< 0.0001
apoB (g/L)	1.21 (0.27)	1.28 (0.28)	1.15 (0.26)	< 0.0001
apoB/apoA-1	0.79 (0.22)	0.87 (0.21)	0.72 (0.20)	< 0.0001

Figure 2. Ranked association of measured and Friedewald (FW)-estimated parameters and extended Friedewald (EFW) estimates with (A) incident non-fatal cardiovascular events (brain, cardiac, peripheral vascular event/procedure), (B) cardiovascular mortality according to Cox regression proportional hazards survival analysis adjusted with age, gender (model 1: upper panels) and age, gender, hypertension, diabetes, current smoking, and lipid-lowering medication (model 2: lower panels). Variables were scaled to zero mean and unit SD before Cox regression analysis. Data are presented as standardized hazard ratios per 1 SD increase.

Figure 3. Ranked net reclassification improvement (NRI) of measured and Friedewald (FW)-estimated parameters and extended Friedewald (EFW) estimates with (A) incident non-fatal cardiovascular events (brain, cardiac, peripheral vascular event/procedure), (B) cardiovascular mortality relative to standard model adjusted with age, gender, hypertension, diabetes, current smoking, and lipid-lowering medication (model 2).

Table II. Ranked net reclassification improvement (NRI) of measured and Friedewald (FW)-estimated parameters and extended Friedewald (EFW) estimates with incident non-fatal cardiovascular events (brain, cardiac, peripheral vascular event/procedure). Cox regression proportional hazards survival analysis adjusted for age, gender, hypertension, diabetes, current smoking, and lipid-lowering medication. C-statistic, Hosmer–Lemeshow chi-square (H-L χ²).

Incident cardiovascular events	C-stat	H-L χ^2	NRI (95% CI) (%)
FW/Established risk factors (model 2) added with:	0.831	18.3	reference
apoB/apoA-I	0.838	9.8	26.0 (12.0, 39.9)
TC/HDL-C	0.837	14.0	25.4 (11.5, 39.4)
apoB	0.836	9.1	24.9 (10.9, 38.8)
apoA-I	0.839	15.4	24.1 (10.2, 38.1)
LDL-C/HDL-C	0.838	13.3	23.5 (9.5, 37.5)
TG	0.835	9.8	16.8 (2.9, 30.8)
HDL-C	0.837	13.2	15.1 (1.2, 29.1)
non-HDL-C	0.835	6.4	11.2 (–2.7, 25.2)
LDL-C	0.836	9.5	7.2 (–6.7, 21.2)
TC	0.835	14.4	4.7 (–9.2, 18.6)
EFW-estimated established risk factors (model 2) added with:	0.831	18.3	reference
apoB	0.837	11.8	25.2 (10.9, 39.5)
IDL-C	0.836	10.1	23.0 (9.0, 36.9)
apoB/apoA-I	0.839	14.0	20.6 (6.3, 35.0)
VLDL-TG	0.835	8.5	20.1 (6.1, 34.0)
HDL2-C	0.833	11.5	16.5 (2.2, 30.8)
apoA-I	0.840	16.0	15.2 (0.9, 29.5)
HDL3-C	0.833	15.8	6.3 (–8.0, 20.6)
EFW-LDL-C	0.835	11.4	1.3 (–12.7, 15.2)

Table III. Ranked association net reclassification improvement (NRI) of measured and Friedewald (FW)-estimated parameters and extended Friedewald (EFW) estimates with cardiovascular mortality. Cox regression proportional hazards survival analysis adjusted for age, gender, hypertension, diabetes, current smoking, and lipid-lowering medication. Variables were scaled to zero mean and unit SD before Cox regression analysis. C-statistic, Hosmer–Lemeshow chi-square (H-L χ²). Infinite value (∞) due to low number of cases.

Cardiovascular mortality	C-stat	H-L χ^2	NRI (95% CI) (%)
FW/Established risk factors (model 2) added with:	0.878	∞	reference
non-HDL-C	0.887	∞	74.9 (39.6, 110.2)
apoB/apoA-I	0.884	∞	63.5 (28.2, 98.8)
TC/HDL-C	0.883	∞	60.8 (25.5, 96.1)
TC	0.884	∞	60.0 (24.6, 95.3)
LDL-C/HDL-C	0.881	∞	59.4 (24.1, 94.7)
apoB	0.893	∞	57.4 (22.1, 92.7)
LDL-C	0.882	∞	55.2 (19.9, 90.5)
TG	0.877	∞	16.0 (–19.3, 51.3)
HDL-C	0.874	∞	10.8 (–24.6, 46.1)
apoA-I	0.872	∞	1.0 (–34.3, 36.3)
EFW-estimated established risk factors (model 2) added with:	0.878	∞	reference
apoB	0.890	∞	25.2 (10.9, 39.5)
IDL-C	0.881	∞	23.0 (9.0, 36.9)
EFW-LDL-C	0.876	∞	20.6 (6.3, 35.0)
apoB/apoA-I	0.880	∞	20.1 (6.1, 34.0)
VLDL-TG	0.878	∞	16.5 (2.2, 30.8)
apoA-I	0.872	∞	15.2 (0.9, 29.5)
HDL2-C	0.878	∞	6.3 (–8.0, 20.6)
HDL3-C	0.879	∞	1.3 (–12.7, 15.2)

Figure 4. Ranked net reclassification improvement (NRI) of measured and Friedewald (FW)-estimated parameters and extended Friedewald (EFW) estimates with (A) incident non-fatal cardiovascular events (brain, cardiac, peripheral vascular event/procedure), and (B) cardiovascular mortality relative to standard model based on Framingham risk score (26) for 10-year cardiovascular risk (model 3).

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