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

Abstract

Introduction: Primary dyslipidemias are inherited disorders in plasma lipoprotein metabolism that lead to serious cardiovascular and other complications. The Japanese Ministry of Health, Labor and Welfare (MHLW) covers medical expenses, under the Research Program on Rare and Intractable Diseases, for homozygous familial hypercholesterolemia (FH), familial chylomicronemia, sitosterolemia, cerebrotendinous xanthomatosis, lecithin:cholesterol acyltransferase deficiency, Tangier disease, and abetalipoproteinemia. Apolipoprotein A1 deficiency, heterozygous FH, and type III hyperlipoproteinemia are covered by the MHLW Pediatric Chronic Disease Program.Heterozygous FH and type III hyperlipoproteinemia are also important for their relatively common prevalence and, accordingly, high impact on Japanese public health by significant contribution to the overall prevalence of cardiovascular diseases. Therefore, a systemic survey of these diseases is mandatory to estimate their actual situation, such as prevalence, clinical manifestations, and prognoses among the Japanese population. The impact of these rare and intractable diseases on cardiovascular and other complications will likely be higher among Japanese people than other ethnicities because the general Japanese population has many cardioprotective aspects. The current study intends to conduct a multicenter registry of these diseases to assess their demographics and clinical features comprehensively. Methods and Analysis:The Prospective Registry Study of Primary Dyslipidemia is a registry-based prospective, observational, multicenter cohort study in Japan, enrolling patients who fulfill the Japanese clinical criteria of the primary dyslipidemias listed above, from 26 participating institutes from August 2015 to March 2023. A total of 1,000 patients will be enrolled in the study and followed for 10 years. Clinical parameters are collected, including physical and laboratory findings, genetic analysis, drugs, lifestyle management, and clinical events, especially cardiovascular events. The primary endpoint of this study is the new onset of cardiovascular disease and acute pancreatitis, and the secondary endpoint is death from any causes. Ethics and Dissemination:This study complies with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. The institutional review boards have approved this study protocol at all participating institutes. The final results are to be published at appropriate international conferences and in peer-reviewed journals.

Clinical Characteristics of Homozygous Familial Hypercholesterolemia in Japan

“…In this regard, another multicenter registry, the Committee on Primary Dyslipidemia of the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour, and Welfare of Japan, conducted a study on HoFH to thoroughly evaluate its genotypes and phenotypes. 31 This study will provide insights into the clinical management of HoFH in the future.…”

The first Japanese case with familial combined hypolipidemia without any complications caused by loss-of function variants in ANGPTL3: Case report

“…However, it is obvious that this is completely independent of LDL receptor pathway, because ANGPTL3 inhibitor appears to reduce serum LDL cholesterol among patients with homozygous familial hypercholesterolemia (FH) regardless of their residual LDL receptor function [ 6 ]. Now, we have been operating a Nation-wide registry for primary dyslipidemias, including FH, ABL, and FHBL since 2015 in Japan [ [17] , [18] , [19] , [20] ]. We are expecting to see there are more individuals with ABL and FHBL who are currently considered as extremely rare disorders.…”

Transitional Medicine of Intractable Primary Dyslipidemias in Japan

“…Since there was no long-term nationwide registry study of primary dyslipidemia conducted, the realistic prognosis of these diseases is not fully understood. A registry study of the (PROLIPID study, see below) finally started in 2015 4) .…”

“…The Prospective registry study of primary dyslipidemia (PROLIPID) study aims to clarify the natural history, medical care, and treatment of primary dyslipidemia 4) . Enrollment of patients with FH, type I I I h y p e r l i p o p r o t e i n e m i a , a n d p r i m a r y hyperchylomicronemia began in 2015, followed by enrollment of patients with sitosterolemia and CTX in 2019, and LCAT deficiency, Tangier disease, and ABL in 2020.…”