Abstract 17461: Major Cardiovascular Events and Liver Disease in Patients With Truncating Variants in APOB and PSCK9

• Published in: Circulation (New York, N.Y.) Vol. 148; no. Suppl_1
• Main Authors: Knight, Stacey, Le, Viet T, Walton, Nephi A, Christensen, G B, Evans, Jared M, May, Heidi T, Anderson, Jeffrey L, Nadauld, Lincoln, Knowlton, Kirk U
• Format: Journal Article
• Language: English
• Published: 07.11.2023
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.148.suppl_1.17461

Abstract only Introduction: Truncated variants in the genes ApoB and PSCK9 have been shown to be associated with low levels of low-density lipoprotein cholesterol (LDL-C), however, there is concern about the increased risk of liver disease. Using Intermountain Health’s HerediGene Population Study, a population-based genetic study, we sought to understand the impact of these variants on major adverse cardiovascular events (MACE) and liver disease. Methods: Of the 32,159 sequenced patients (pts), 58 (0.18%) had a truncating variant in ApoB (n=49) and PCSK9 (n=10). Among those with a truncating variant, we compared the demographics, LDL-C levels, statin use, and disease by MACE (including, myocardial infarction [MI], heart failure (HF) hospitalization, stroke, peripheral artery disease, and carotid artery disease). Results: MACE occurred in 32% of pts, with HF hospitalization followed by MI being the most frequent. The rates of MACE were similar for pts with ApoB (n=15, 30.6%) and PCSK9 (n= 4, 40%). Differences in demographics and clinical characteristics stratified by MACE are shown in the Table. LDL-C levels were low in both groups, with approximately half having an LDL-C <70 mg/dL. Hypertension was more common in the MACE group (95% vs 50%). Both groups had high rates of liver disease (47%) compared to the general patient population (9%). Renal failure was also common among these pts (36%). Only 2 of the deaths (both in the MACE group) were cardiovascular-related, 1 due to stroke and 1 due to heart failure. Conclusion: Low LDL-C was associated with truncated variants in the ApoB and PSCK9 genes. However, these patients still had a high rate of MACE, which was driven mainly by hypertensive diseases. Frequency of liver disease and renal failure was high, which may also be attributed to hypertension. While this is a small sample, these findings suggest that continued screening for cardiovascular disease is needed despite low LDL-C, with liver disease screening also needing to be performed.