Aims: A large proportion of ischemic cardiovascular disease occur in people without hypercholesterolemia. We aimed to investigate whether risk factors other than low-density lipoprotein cholesterol (LDL-C) have different impacts on cardiovascular risk in people with low verses high LDL-C levels. Methods: A total of 30,378 participants (35-64 years) were followed for 15 years in the Chinese Multi-provincial Cohort Study. Associations of coronary heart disease (CHD) and ischemic stroke with risk factors other than LDL-C were assessed in participants with low (<130 mg/dL) and high (>= 130 mg/dL) LDL-C levels. Results: During the follow-up, 65.5% of CHD and 70.2% of ischemic stroke events occurred in participants with low LDL-C. High triglycerides predicted CHD (HR = 1.74, 95% CI 1.25-2.42, P = 0.001), and low HDL-C predicted ischemic stroke (HR = 1.54, 95% CI 1.18-2.03, P = 0.002) only in participants with low LDL-C. Diabetes predicted CHD in participants with high LDL-C (HR = 2.38, 95% CI 1.31-4.34, P = 0.005), but not in those with low LDL-C. Older age, male, hypertension, central obesity, and smoking had similar effects on the risk in both groups. Conclusions: Triglycerides and low HDL-C should be addressed in the management of dyslipidemia in people with low LDL-C. When LDL-C is high, tighter management of glycemia and LDL-C is warranted. (C) 2012 Elsevier Ireland Ltd. All rights reserved.