The baseline characteristics for individuals randomly allocated to receive rosuvastatin and who had on-treatment lipid and lipoprotein measurements available for analysis at baseline and one-year were similar to the overall JUPITER study population.17,20
The JUPITER patients were selected to have an LDL-C <130 mg/dL and triglycerides <500 mg/dL, and hence the total cholesterol, LDL-C, and non-HDL cholesterol were all low (respective median baseline concentrations of 186, 108, and 134 mg/dL). The apolipoprotein B levels were not low (median baseline concentration 109 mg/dL). Random allocation to rosuvastatin in the JUPITER trial decreased median on-treatment concentrations of total, LDL, and non-HDL-C to a similar extent on a mass concentration scale (−50 mg/dL, −50 mg/dL, and −54 mg/dL, respectively) and reduced apolipoprotein B by 41 mg/dL (). There was greater proportional LDL-C lowering (46.2%) compared with non-HDL-C (40.3%) or apolipoprotein B (37.6%) with rosuvastatin therapy. Triglycerides were also reduced, but to a lesser extent.
Median, 25th, and 75th percentile values for lipids, apolipoproteins, and ratios among 7,832 rosuvastatin-treated individuals with baseline and 1-year measures of all lipid variables examined
The primary endpoint was reduced with rosuvastatin by 44% (P<0.001).17
shows CVD incidence rates and associations for each of the on-treatment lipids, apolipoproteins, and ratios (examined in tertiles) with incident events obtained from separate Cox regression models that adjusted for non-lipid risk factors. Generally similar and significant associations were obtained for on-treatment concentrations of LDL-C, non-HDL-C, and apolipoprotein B with CVD. By contrast, on-treatment triglycerides, HDL-C, and apolipoprotein A-1 showed no associations with CVD risk. Similar results were noted for the expanded secondary endpoint of CVD or death, except that apolipoprotein A-1 now became statistically significant and the apolipoprotein B/A-1 ratio now had a greater magnitude of association (2.12, 95 % CI 1.44–3.12).
Risk of first CVD event or death for on-treatment lipids, apolipoproteins, and ratios by tertiles
When lipids, apolipoproteins, and ratios were examined as standardized continuous variables, results were generally similar for LDL-C, non-HDL-C, apolipoprotein B, and the ratios (), as were the goodness-of-fit likelihood ratio χ2 statistics that added each of these variables to a model with only non-lipid risk factors. Specifically, for on-treatment LDL-C, non-HDL-C, apolipoprotein B, and the ratios, total/HDL-C, LDL-C/HDL-C, and apolipoprotein B/A-1, the respective adjusted standardized hazard ratios (95% CIs) were 1.31 (1.09–1.56), 1.25 (1.04–1.50), 1.27 (1.06–1.53), 1.22 (1.03–1.44), 1.29 (1.09–1.52), and 1.27 (1.09–1.49).
Risk of first CVD event or death for standardized on-treatment lipids, apolipoproteins, and ratios
We then conducted two exploratory analyses. First, we assessed whether any of the measures non-HDL-C, apolipoprotein B, total/HDL-C, LDL-C/HDL-C, or apolipoprotein B/A-1 was significantly related to residual risk after controlling for on-treatment LDL-C. In models that included on-treatment LDL-C, none of the other lipid measures remained statistically significant.
Subsequently, we compared associations with residual risk among the subgroups of individuals who achieved the clinical recommendations for LDL-C targets, or the alternative recommended targets for non-HDL-C or apolipoprotein B. As shown in , among the subgroups of individuals achieving the lower clinical targets (LDL-C ≤70 mg/dL, non-HDL-C ≤100 mg/dL, or apolipoprotein B ≤80 mg/dL), the magnitude of residual risk was small and the residual risk associated with these measures became attenuated and mostly no longer statistically significant. Apolipoprotein B/A-1 retained its association with the expanded secondary endpoint of CVD or death, but this was also attenuated in the subgroup of individuals who achieved apolipoprotein B ≤80 mg/dL on therapy.
Risk of first CVD event or death for standardized on-treatment lipids, apolipoproteins, and ratios by subgroups