Objectives Atherosclerosis progression in human arteries is still not entirely clear. Several cohort studies have investigated the baseline risk factors associated with future carotid plaque formation, but few prospective study has investigated the associations between risk factor changes and the progression of carotid plaque. Therefore, we conducted a cohort study in the Chinese population to evaluate the effect of 5-year (2002-2007) changes in multiple risk factors on the progression of carotid atherosclerosis.
Methods This study population included 2063 Chinese individuals (1245 women and 818 men, aged from 38-74 years) who underwent twice B-mode ultrasound examinations of carotid arteries in 2002 and 2007. The progression of carotid atherosclerosis was defined as the appearance of at least one plaque at reexamination in a previously plaque-free arterial segment. The Modified Poisson Regression was performed to build two models: one based on baseline risk factor status (Modelbase), and the other based on baseline status and 5-year change in status (Modelbase + change). Population attributable risk (PAR) was calculated according to the methods proposed by Spiegelman et al. Receiver operating characteristic (ROC) curve analysis was used to compare the two models in their ability to predict 5-year progression and equality of the area under the curves (AUC, or c-statistics) was tested using the algorithm proposed by DeLong et al. We also used the net reclassification improvement (NRI) index proposed by Pencina et alto evaluate the additive value of Modelbase + change beyond Modelbase.
Results Modelbase indicated that baseline age, smoking, hypertension, high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and diabetes were all significantly associated with plaque progression; the summarised population attributable risk (PAR) was 28.4%. Modelbase + change indicated that status changes in age, hypertension, and high LDL-C were significant; the summarised PAR was 37.9%. Compared with Modelbase, Modelbase + change exhibited a significant increase in c-statistics (P = 0.001), from 0.668 (95% CI: 0.645-0.691) to 0.688 (95%CI: 0.665-0.710). The NRI was 2.17% (95% CI: 1.29-3.05, P = 0.073) among participants without atherosclerosis progression, and was 6.57% (95% CI: 5.04-8.11, P < 0.001) among those with progression. The summarised NRI was 8.74 (95% CI: 7.51-9.94, P < 0.001). Adverse change in hypertension and elevated LDL-C accelerated atherosclerosis progression, but favourable change in their status failed to slow progression. We further explored whether hypertension status modified the association between change in LDL-C status and carotid atherosclerosis progression. In stratified analysis, favourable change in LDL-C status significantly decreased the progression rate only among participants without hypertension at both examinations (RR = 0.50, 95% CI: 0.35-0.73, P < 0.001).
Conclusions Our study results demonstrated that 5-year changes in a set of risk factors were independently associated with atherosclerosis progression, and could provide modest predicted value beyond baseline risk factors. In addition, we found that the risk of atherosclerosis progression associated with LDL-C was reversible only when blood pressure maintained normal.