Author + information
- Matthew Mefford,
- Robert Rosenson,
- Mary Cushman,
- Michael Farkouh,
- Leslie McClure,
- Virginia Wadley,
- Monika Safford,
- Ransi Somaratne,
- Keri Monda and
- Emily Levitan
Background: An imbalance of adverse neurocognitive events have been reported in early post-hoc analyses of randomized trials of pharmacologic PCSK9 inhibition for LDL-C reduction. We examined the association between PCSK9 loss-of-function (LOF) variants and neurocognitive impairment.
Methods: Neurocognitive impairment, defined as a score ≥1.5 SD below age, sex, and education-based stratum-specific means on 2 of 3 Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery assessments (Word List Learning, Delayed Recall, Semantic Fluency) and separately a score<5 on any Six Item Screener (SIS) assessment, was investigated among African American REGARDS participants with (n =241) and without (n =10,454) PCSK9 LOF variants C697X or Y142X. Odds ratios (OR) and 95% confidence intervals (CI) for neurocognitive impairment associated with PCSK9 LOF variants were estimated adjusting for number of times cognitive function was assessed, age, and other risk factors for neurocognitive impairment.
Results: The mean age was 64 (9.2) years old and 61.7% were female. In participants with versus without PCSK9 LOF variants, mean LDL-C was lower (84 mg/dL vs 117 mg/dL) and statin use was less common (13.3% vs 29.7%). Neurocognitive impairment was detected in 1,962 participants (18.4%) over 9 years of follow-up with participants completing an average of 3 waves of CERAD assessments. The percentage of participants with neurocognitive impairment was similar between those with versus without PCSK9 LOF variants (18.3% vs 18.4% either CERAD or SIS definition). After multivariable adjustment, the odds ratio for neurocognitive impairment associated with a PCSK9 LOF variant was 1.13 (95% CI 0.59, 2.17) and 0.89 (95% CI 0.61, 1.30) using the CERAD and SIS definitions of impairment, respectively.
Conclusions: We found no association between PCSK9 LOF variants and neurocognitive impairment as assessed by two validated measures.
Room 147 A
Sunday, March 19, 2017, 8:12 a.m.-8:22 a.m.
Session Title: Highlighted Original Research: Prevention and the Year in Review
Abstract Category: 32. Prevention: Clinical
Presentation Number: 911-04
- 2017 American College of Cardiology Foundation