Abstract 6282: Lowered Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol with Lipid lowering therapy Associated with Reduction of Cardiovascular Events in Primary Prevention: MEGA Study Post-hoc Analysis
Background. Recently, it was reported that lowering the ratio of low-density lipoprotein cholesterol (LDL) to high-density lipoprotein cholesterol (HDL) [LDL/HDL ratio] with lipid lowering therapy is associated with coronary atheroma regression. However, there is limited information regarding the relation between cardiovascular events and LDL/HDL ratio reduction. Moreover, it remains unclear whether this ratio reduction applies to patients with high HDL, who have a proportionally higher LDL level, even persons with a low LDL/HDL ratio level.
Methods. The MEGA Study evaluated the effect of low dose pravastatin (10 –20 mg/day) on primary prevention of cardiovascular disease in 7,832 Japanese patients (men 40 to 70 years; women post-menopause to 70 years) with mild to moderate hyperlipidemia without cardiovascular disease. Patients were randomized to diet alone or diet plus pravastatin and followed for more than 5 years. On-treatment LDL and HDL levels in each patient were determined by averaging all measurement during follow-up. The incidence of all cardiovascular events was compared according to on-treatment LDL/HDL ratio level, using the Cox proportional hazard model adjusted for sex, age, hypertension, diabetes, and smoking. The incidence of cardiovascular events was also compared according to the on-treatment LDL/HDL ratio level in the patients with high on-treatment HDL (≥60 mg/dL).
Results. The LDL levels decreased from a mean of 155.9 to 139.1 mg/dL, HDL levels were increased from a mean of 57.5 to 59.5 mg/dL, and the LDL/HDL ratio changed from a mean of 2.9 to 2.5 during the study periods. A linear relation was found between the on-treatment LDL/HDL ratio and the incidence of all cardiovascular events; the hazard ratio (HR) was 1.5 for a ratio between 2.0 to <2.5, HR 2.4 for 2.5 to <3.0 ratio, and HR 2.6 for a ratio ≥3.0, compared to a ratio of <2.0 (Trend P<0.001). A similar trend was seen in the high HDL group [HR 1.4 for ratio between 2.0 to <2.5, HR 2.7 for ratio ≥2.5, compared to <2.0 (Trend P=0.035)].
Conclusion. Lowering the LDL/HDL ratio by lipid lowering therapy is associated with a lower incidence of cardiovascular disease events in the setting of primary prevention. These findings are applicable even in patients with a high HDL level.