ABCA1 gene variation and heart disease risk reduction in the elderly during pravastatin treatment

- Effects of ABCA1 R219K variant on cardiac endpoints on PROSPER trial were examined.
- Baseline HDL cholesterol associated with the variant, but LDL cholesterol did not.
- The variant did not associate with LDL lowering response or CHD at baseline.
- The hazard ratio for new events of the variant in the pravastatin group was 1.41.
- The ABCA1 R219K variant may get significantly less risk reduction from pravastatin.

AimsOur goals were to examine the relationships of a specific ATP-binding cassette transporter A1 (ABCA1) variant, rs2230806 (R219K), on baseline lipids, low-density lipoprotein cholesterol (LDL-C) lowering due to pravastatin, baseline heart disease, and cardiac endpoints on trial.Methods and resultsThe ABCA1 R219K variant was assessed in 5414 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and followed for a mean of 3.2 years. Of these subjects 47.6% carried the variant, with 40.0% carrying one allele, and 7.6% carrying both alleles. No effects on baseline LDL-C levels were noted, but mean HDL-C increased modestly according to the number of variant alleles being present (1.27 vs 1.28 vs 1.30 mmol/L, p = 0.024). No relationships between the presence or absence of this variant and statin induced LDL-C lowering response or CHD at baseline were noted. However within trial those with the variant as compared to those without the variant, the overall adjusted hazard ratio for new cardiovascular disease (fatal CHD, non-fatal myocardial infarction, or fatal or non-fatal stroke) was 1.22 (95% CI 1.06-1.40, p = 0.006), while for those in the pravastatin group it was 1.41 (1.15-1.73, p = 0.001), and for those in the placebo group it was 1.08 (0.89-1.30, p = 0.447) (p for interaction 0.058).ConclusionOur data indicate that subjects with the ABCA1 R219K variant may get significantly less heart disease risk reduction from pravastatin treatment than those without the variant.