The effect of achieving LDL-C <1.8 mmol/L to prevent the first atherosclerotic cardiovascular events in the primary prevention settings of severe heterozygous familial hypercholesterolemia. (3rd October 2022)

• Record Type: Journal Article
• Authors: Funabashi, S; Kataoka, Y; Hori, M; Ogura, M; Doi, T; Noguchi, T; Shiba, M
• Is Part Of: European heart journal. Volume 43(2022)Supplement 2
• Publication Date: 2022-10-03
• Subjects: Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac544.2344
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Introduction: The International Atherosclerosis Society (IAS) has proposed &quot;severe familial hypercholesterolemia&quot; (FH) as a phenotype with the highest cardiovascular risk. LDL-C &lt;2.5 mmol/l is a recommended therapeutic goal for the primary prevention settings of severe FH. However, given that ESC guidelines recommends LDL-C &lt;1.8 mmol/l in FH patients, this stricter goal may be better to prevent the first atherosclerotic cardiovascular disease (ASCVD) in severe FH patients. Purpose: To determine whether achieving LDL-C&lt;1.8 mg/dl is more beneficial to reduce the first ASCVD events. Methods: A total of 148 severe FH subjects without any history of ASCVD were analyzed. Severe FH was defined as untreated LDL-C &gt;10.3 mmol/l, LDL-C &gt;8.0 mmol/l+ 1 high-risk feature, LDL-C &gt;4.9 mmol/l + 2 high-risk features according to IAS proposed statement. The occurrence of ASCVD (all-cause death, CAD, ischemic stroke and lower extremity artery disease (LEAD)) were compared in those with on-treatment LDL-C &lt; and ≥1.8 mmol/L. Results: 10.1% (=15/148) of study subjects achieved on-treatment LDL-C &lt;1.8 mmol/l. They were more likely to receive PCSK9 inhibitor (15.0 vs. 66.7%, p&lt;0.01), whereas there was no significant difference in FH-related physical characteristics (tendon xanthomas: 72.2 vs. 93.3%, p=0.12) and causative genotypes (LDLR: 68.4 vs. 66.7%, p=1.00, PCSK9: 8.3 vs. 6.7%, p=1.00, LDLR/PCSK9: 3.8 vs. 6.7%, p=0.48), untreated LDL-C (7.3±1.7 vs. 7.9±1.8 mmol/l, p=0.22) and lipoprotein(a) (23 [11–42] vs. 25 [15–70] mg/dl, p=0.41) levels between two groups. During the observational period (median=7.0 years), severe FH achieving on-treatment LDL-C &lt;1.8 mmol/l was associated with a lower likelihood of experiencing ASCVD events (Figure 1). Of note, any cardiovascular events did not occur in severe FH who achieved on-treatment LDL-C &lt;1.8 mmol/l. In those with on-treatment LDL ≥1.8 mmol/L, CAD (76.5%=26/34) was more dominant component of ASCVD, followed by ischemic stroke (17.6%=6/34) and LEAD (5.9%=2/34). Conclusions: A significantly lower frequency of ASCVD was observed in severe FH who achieved LDL-C &lt;1.8 mmol/L in the primary prevention settings. Given that only 10.1% of severe FH patients achieved LDL-C &lt;1.8 mmol/l, more actions are required to motivate physicians for further intensified management of LDL-C in severe FH patients in the primary prevention settings. Funding Acknowledgement: Type of funding sources: None.