Relation of Serum Lipoprotein(a) Levels to Lipoprotein and Apolipoprotein Profiles and Atherosclerotic Diseases in Japanese Patients with Heterozygous Familial Hypercholesterolemia: Familial Hypercholesterolemia Expert Forum (FAME) Study

Abstract

The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Original Article Aims: Lipoprotein(a) [Lp(a)] is a plasma lipoprotein consisting of a low-density lipoprotein (LDL)-like particle with apolipoprotein (Apo)(a), attached via a disulfide bond to Apo B100. Previous studies have shown that high Lp(a) levels are associated with an increased risk of cardiovascular disease in patients with familial hypercholesterolemia (FH). To date, limited data are available as to distribution of Lp(a) in FH and associations of Lp(a) with other lipid profiles and cardiovascular disease. Our study aimed to investigate serum Lp(a) levels in relation to other lipid profiles and clinical conditions in the national largest-ever cohort of Japanese FH patients. Methods: This study is a secondary analysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study that includes a Japanese nationwide cohort of FH patients. In 399 patients under treatment for heterozygous FH who had a baseline measurement of serum Lp(a), the present study examined the distribution of Lp(a) levels and associations of Lp(a) with other lipid profiles and clinical conditions including coronary artery disease (CAD). Results: The distribution of Lp(a) was skewed to the right with a median of 20.8 mg/dL, showing a log-normal distribution. Serum Apo B and Apo E levels were positively associated with Lp(a) levels. Age-adjusted mean of Apo B was 8.77 mg/dL higher and that of Apo E was 0.39 mg/dL higher in the highest category (40+ mg/dL) of Lp(a) than in the lowest category ( 20 mg/dL). LDL-C levels did not show such an association with Lp(a) levels. A tendency towards a positive relationship between Lp(a) and prevalent CAD was observed in men. Conclusion: Our study demonstrated a distribution pattern of Lp(a) in Japanese FH patients and positive relationships of Lp(a) with Apo B and Apo E levels.consisting of a low-density lipoprotein (LDL)-like particle with one additional protein, apolipoprotein(a), attached via a disulfide bond to apolipoprotein B100 1) .

Assessment of Associations Between Serum Lipoprotein (a) Levels and Atherosclerotic Vascular Diseases in Hungarian Patients With Familial Hypercholesterolemia Using Data Mining and Machine Learning

“…Our results are in line with these results. Recently, lower mean Lp(a) levels were found in a Japanese cohort (20.8 mg/dl; 208 mg/L) ( Naito et al, 2021 ) and in a previous other Japanese study (21.9 mg/dl; 219 mg/L) ( Tada et al, 2018 ), demonstrating the importance of racial differences. Significantly increased Lp(a) levels in females were previously described in FH ( Alonso et al, 2008 ), as well as in patients with CVD ( Virani et al, 2012 ) and PAD ( Forbang et al, 2016 ), and in the general population ( Banerjee et al, 2011 ).…”

Synergistic effect of lipoprotein (a) and C-reactive protein on prognosis of familial hypercholesterolemia

“…When there is an innately elevated serum Lp(a) level, the association between Lp(a) and CVD events among patients with FH produces controversial results [ [28] , [29] ]. Several studies among general populations have suggested that Lp(a) and CRP appear to have synergistic effects in the development of CVD events [ [11] , [12] ].…”

Prospective Registry Study of Primary Dyslipidemia (PROLIPID): Rationale and Study Design

“…Due to their rarity, the accumulation of the data of these intractable diseases is not adequate for their natural history, current clinical situations, and factors associated with prognosis. However, several large scale registry studies have clarified some useful clinical information and genetic backgrounds [23][24][25][26][27][28][29] . Therefore, it is essential to understand the unique profiles of these diseases in Japan for frequency, phenotype, and genotype and their clinical prognosis, hopefully, based on the registration of all the patients, to help useful feedback to the current guidelines for their diagnosis and management.…”