Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease. Insights from the Incremental Decrease in End-points through Aggressive Lipid-lowering Trial (IDEAL)

Figures & data

Table I.  Mean (SD) of base-line and average 12- and 24-week lipoprotein parameters (n=8564).

		Average of 12 and 24 weeks
Lipoprotein parameters	Base-line	Simvastatin	P-value versus base-line	Atorvastatin	P-value versus base-line
TC (mmol/L)	5.08 (1.01)	4.64 (0.76)	<0.001	3.80 (0.77)	<0.001
LDL-C (mmol/L)	3.14 (0.89)	2.72 (0.64)	<0.001	2.03 (0.62)	<0.001
HDL-C (mmol/L)	1.19 (0.31)	1.23 (0.31)	<0.001	1.18 (0.30)	<0.001
Non-HDL-C (mmol/L)	3.88 (1.00)	3.41 (0.74)	<0.001	2.59 (0.71)	<0.001
ApoB (g/L)	1.19 (0.32)	1.06 (0.25)	<0.001	0.81 (0.24)	<0.001
ApoA-1 (g/L)	1.39 (0.22)	1.42 (0.22)	<0.001	1.36 (0.21)	<0.001
LDL-C/HDL-C	2.78 (1.08)	2.35 (0.83)	<0.001	1.82 (0.68)	<0.001
TC/HDL-C	4.50 (1.41)	3.98 (1.06)	<0.001	3.35 (0.89)	<0.001
ApoB/apoA-1	0.88 (0.29)	0.77 (0.23)	<0.001	0.61 (0.20)	<0.001

TC = total cholesterol; LDL-C = low-density lipoprotein; HDL = high-density lipoprotein; Non-HDL-C = TC minus HDL-C; apoB = apolipoprotein B; apoA-1 = apolipoprotein A-1; SD = standard deviation.

Table II.  Log likelihood chi-square statistics of MCE risk from 6 months onwards from Cox proportional hazards model and hazard ratios for 1 SD decrease with single lipoprotein parameters measured as average of 12 and 24 weeks, each adjusted for age, sex, and smoking.

Lipoprotein parameters	Chi-square statistic	Chi-square added	HR 1SD decr (95% CI)	P-value
Adjustment factors alone	89.9	–	–	–
TC	100.0	10.1	0.88 (0.82–0.95)	<0.0001
LDL-C	102.9	13.0	0.87 (0.81–0.94)	<0.0001
Non-HDL-C	106.5	16.6	0.86 (0.80–0.92)	<0.0001
ApoB	109.7	19.8	0.85 (0.79–0.91)	<0.0001
HDL-C	94.2	4.3	1.09 (1.00–1.18)	0.04
ApoA-1	96.6	6.7	1.11 (1.02–1.20)	0.01
LDL-C/HDL-C	110.9	21.0	0.87 (0.83–0.92)	<0.0001
TC/HDL-C	112.0	22.1	0.84 (0.79–0.90)	<0.0001
ApoB/apoA-1	119.7	29.8	0.83 (0.77–0.88)	<0.0001

TC = total cholesterol; LDL-C = low-density lipoprotein; HDL = high-density lipoprotein; Non-HDL-C = TC minus HDL-C; apoB = apolipoprotein B; apoA-1 = apolipoprotein A-1; MCE = major coronary event; SD = standard deviation; HR 1SD = hazard ratio for 1 SD decrease; CI = confidence interval.

Figure 1.  Added chi-square information value of each lipoprotein component on major coronary event (MCE) over and above age, gender, and smoking, ranked according to importance. For abbreviations see footnotes to Table II.

Figure 2.  Hazard ratio (HR) of major coronary event (MCE) with 95% CI by quintiles of in-trial LDL-C (Panel A) and apoB (Panel B), adjusted for age, gender, and smoking.

Table III.  Model comparisons of joint versus single variable chi-square statistics for MCE, adjusted for age, gender, and smoking.

	Chi-square difference	P-value
(LDL-C + apoB) versus apoB	110.4–109.7 = 0.7	NS
(LDL-C + apoB) versus LDL-C	110.4–02.9 = 7.5	<0.01
(HDL-C + apoA-1) versus apoA-1	96.9–96.3 = 0.6	NS
(HDL-C + apoA-1) versus HDL-C	96.9–94.2 = 2.7	0.10
(LDL-C/HDL-C + apoB/apoA-1) versus apoB/apoA-1	120.3–119.7 = 0.6	NS
(LDL-C/HDL-C + apoB/apoA-1) versus LDL-C/HDL-C	120.3–110.9 = 9.4	<0.001
(TC/HDL-C + apoB/apoA-1) versus apoB/apoA-1	119.9–119.7 = 0.2	NS
(TC/HDL-C + apoB/apoA-1) versus TC/HDL-C	119.9–112.0 = 7.9	<0.01
(ApoB + apoA-1 + apoB/apoA-1) versus apoB/apoA-1	120.1–119.7 = 0.4
(LDL-C + HDL-C + apoB + apoA-1 + apoB/apoA-1) versus apoB/apoA-1	124.5–119.7 = 4.8	NS (DF = 4)

TC = total cholesterol; LDL-C = low density lipoprotein; HDL-C = high density lipoprotein; apoB = apolipoprotein B; apoA-1 = apolipoprotein A-1; MCE = major coronary event; NS = not significant; DF = degrees of freedom of chi square

Table IV.  Estimated MCE hazard ratio (95% CI) from 6 months onwards of atorvastatin versus simvastatin from observed DELTA with per cent of estimated relative risk reduction out of observed. Adjustments are made for age, gender, and smoking.

	Between group difference in change from base-line
Lipoprotein parameters	Absolute	In SD units	Predicted MCE HR (95% CI)	RRR%	% of observed RRR
TC (mmol/L)	0.844	0.933	0.888 (0.826–0.953)	11.8	80.0
LDL-C (mmol/L)	0.683	0.819	0.880 (0.822–0.942)	12.0	85.7
Non-HDL-C (mmol/L)	0.825	0.896	0.859 (0.800–0.923)	14.1	100.7
ApoB (g/L)	0.254	0.884	0.857 (0.807–0.911)	14.3	102.1
LDL-C/HDL-C	0.535	0.600	0.913 (0.881–0.947)	8.7	62.0
TC/HDL-C	0.655	0.613	0.897 (0.869–0.926)	10.3	73.6
ApoB/apoA-1	0.153	0.663	0.878 (0.838–0.919)	12.2	87.4

TC = total cholesterol; LDL-C = low-density lipoprotein; HDL = high-density lipoprotein; Non-HDL-C = TC minus HDL-C; apoB = apolipoprotein B; apoA-1 = apolipoprotein A-1; MCE = major coronary event; HR = hazard ratio of MCE risk between treatment groups, SD = standard deviation; CI = confidence interval; RRR = relative risk reduction; DELTA = between treatment group difference in change from base-line to average of 12 and 24 week lipoprotein parameters.