Dataset Information

Prevalence, self-awareness, and LDL cholesterol levels among patients highly suspected as familial hypercholesterolemia in a Japanese community.

ABSTRACT: Backgrounds:The prevalence of familial hypercholesterolemia (FH) among Japanese populations is still unclear. In addition, no prior data exist regarding the self-awareness. Accordingly, we aimed to investigate the prevalence, self-awareness, and LDL-C of patients with highly suspected as FH using data obtained in a community-based medical checkups. Methods:This study included 52,276 subjects (18,588 men, 35.6%) aged ?40 years who underwent the Japanese specific health checkup in Kanazawa City during 2018. We assessed the self-awareness of dyslipidemia (and the age) as well as the prevalence of patients with highly suspected as FH whose naïve LDL-C levels were ?250 ?mg/dl. Naïve LDL-C levels were estimated by the adjustment (LDL-C/0.7) for those on lipid-lowering medication. We divided subjects into 3 groups based on their naïve LDL cholesterol level (?250 ?mg/dl, 140-249, and ?139 ?mg/dl). Results:We identified 262 (0.5%) individuals highly suspected as FH whose naïve LDL-C levels were ?250 ?mg/dl. Most of them (234 among 262, 89%) were under lipid-lowering medication; however, the self-awareness as dyslipidemia was not quite high (200 among 262, 76%), and their mean LDL-C level under lipid-lowering medication was 203 ?± ?35 ?mg/dl. Interestingly, the age of acknowledgement of dyslipidemia among the patients with highly suspected as FH was significantly younger than those in other categories (58 vs. 60/62 ?yrs, respectively, p ?< ?0.05 for both). Conclusions:The prevalence of patients highly suspected as FH was around 1 in 200, and their self-awareness as well as control were not still good enough among Japanese general populations.

SUBMITTER: Tada H

PROVIDER: S-EPMC7585140 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Prevalence, self-awareness, and LDL cholesterol levels among patients highly suspected as familial hypercholesterolemia in a Japanese community.

Tada Hayato H Shibayama Junichi J Nishikawa Tetsuo T Okada Hirofumi H Nomura Akihiro A Usui Soichiro S Sakata Kenji K Hashiba Atsushi A Inazu Akihiro A Takamura Masayuki M Kawashiri Masa-Aki MA

Practical laboratory medicine 20201019

<h4>Backgrounds</h4>The prevalence of familial hypercholesterolemia (FH) among Japanese populations is still unclear. In addition, no prior data exist regarding the self-awareness. Accordingly, we aimed to investigate the prevalence, self-awareness, and LDL-C of patients with highly suspected as FH using data obtained in a community-based medical checkups.<h4>Methods</h4>This study included 52,276 subjects (18,588 men, 35.6%) aged ≥40 years who underwent the Japanese specific health checkup in K ...[more]

PMID: 33134467

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Project description:BACKGROUND:Familial hypercholesterolemia (FH) and other extreme elevations in low-density lipoprotein cholesterol significantly increase the risk of atherosclerotic cardiovascular disease; however, recent data suggest that prescription rates for statins remain low in these patients. National rates of screening, awareness, and treatment with statins among individuals with FH or severe dyslipidemia are unknown. METHODS:Data from the 1999 to 2014 National Health and Nutrition Examination Survey were used to estimate prevalence rates of self-reported screening, awareness, and statin therapy among US adults (n=42?471 weighted to represent 212 million US adults) with FH (defined using the Dutch Lipid Clinic criteria) and with severe dyslipidemia (defined as low-density lipoprotein cholesterol levels ?190 mg/dL). Logistic regression was used to identify sociodemographic and clinical correlates of hypercholesterolemia awareness and statin therapy. RESULTS:The estimated US prevalence of definite/probable FH was 0.47% (standard error, 0.03%) and of severe dyslipidemia was 6.6% (standard error, 0.2%). The frequency of cholesterol screening and awareness was high (>80%) among adults with definite/probable FH or severe dyslipidemia; however, statin use was uniformly low (52.3% [standard error, 8.2%] of adults with definite/probable FH and 37.6% [standard error, 1.2%] of adults with severe dyslipidemia). Only 30.3% of patients with definite/probable FH on statins were taking a high-intensity statin. The prevalence of statin use in adults with severe dyslipidemia increased over time (from 29.4% to 47.7%) but not faster than trends in the general population (from 5.7% to 17.6%). Older age, health insurance status, having a usual source of care, diabetes mellitus, hypertension, and having a personal history of early atherosclerotic cardiovascular disease were associated with higher statin use. CONCLUSIONS:Despite the high prevalence of cholesterol screening and awareness, only ?50% of adults with FH are on statin therapy, with even fewer prescribed a high-intensity statin; young and uninsured patients are at the highest risk for lack of screening and for undertreatment. This study highlights an imperative to improve the frequency of cholesterol screening and statin prescription rates to better identify and treat this high-risk population. Additional studies are needed to better understand how to close these gaps in screening and treatment.

Project description:Background: Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals. Methods: Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography ? mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL. Results: Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Conclusion: Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease. Keywords: Micro-array analysis, cell type comparison,

Project description:BackgroundElevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals.MethodsCholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography - mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL.ResultsUsing microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells.ConclusionOur data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

Dataset Information

Prevalence, self-awareness, and LDL cholesterol levels among patients highly suspected as familial hypercholesterolemia in a Japanese community.

Publications

Prevalence, self-awareness, and LDL cholesterol levels among patients highly suspected as familial hypercholesterolemia in a Japanese community.

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