See article vol.29: 1709-1726 Dyslipidemia in Obese Children Blood biochemical abnormal values induced by being overweight are often seen in children and in adults. The most frequent complications in ...obese children are fatty liver, insulin resistance (hyperinsulinemia), and hypertriglyceridemia. The criteria of dyslipidemia for Japanese children (fasting test) have been defined as total cholesterol (TC) levels of >- 220mg/dL, LDL cholesterol (LDL-C) levels of >- 140mg/dL, triglyceride (TG) levels of >- 140mg/dL, HDL cholesterol (HDL-C) levels of < 40mg/dL, and non-HDL-C levels of >- 150mg/dL. The cutoff value of HDL-C is based on the 5th percentile value, and those for other lipids are each on the 95th percentile value. Maeda et al. studied the secular trends in terms of body size and serum lipid levels of 10-year-old children by analyzing a 27-year data from Oita Prefecture in Kyushu, Japan, and showed that the frequency of high TG, low HDL-C, and high non- HDL-C was 4%-7%, 1%-1.5%, and 6%-8%, respectively. The frequency of low HDL-C was lower than the expected value. They also reported that the frequency of high TG, low HDL-C, and high non- HDL-C in obese children, estimated by the percentage of overweight (POW) >- 20%, was 15%-25%, 3%-7%, and 15%-25%, respectively.
To prevent obesity in middle age, early precautions and interventions are required during childhood. Therefore, it is very important to accurately evaluate the degree of overweight in children. Body ...mass index (BMI) is widely used worldwide in adults, but not in children. Because standard BMI, which is calculated using the average height and weight for age, changes widely during growth, a constant cut-off point cannot be set for children. An international unified method defining childhood obesity has not been established. In many countries, BMI-for-age percentile (BMI%) value or Z (standard deviation) score is used, whereas in Japan, the percentage of overweight (POW), which is the modified weight-for-height method, is used. We compared BMI% values with POW values obtained using the anthropometric data of elementary and junior high school students based on the Japanese school survey conducted in 2000 and found that the values for the degree of overweight were significantly different between the two methods. It became clear that tall students were easily defined as being overweight, whereas short students tended to be evaluated as being underweight when using BMI%. POW method seemed to be more appropriate than BMI% for school-age children. Abdominal obesity, excess visceral adipose tissue (VAT), is highly associated with obesity-related complications. Waist circumference (WC) is now accepted as an appropriate guide to VAT accumulation. The cut-off value of WC defining excess VAT is 80 cm at the umbilical level in Japanese school-age children. It is not easy to decide the obesity criteria and optimum WC in school-age children. Childhood obesity should be discussed more internationally.
Homozygous Familial Hypercholesterolemia Nohara, Atsushi; Tada, Hayato; Ogura, Masatsune ...
Journal of Atherosclerosis and Thrombosis,
07/2021, Letnik:
28, Številka:
7
Journal Article
Odprti dostop
Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them ...exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Since LDL receptor activity is severely impaired, HoFH patients do not or very poorly respond to medications to enhance activity, such as statins, and have a poorer prognosis compared to HeFH. HoFH should therefore be clinically distinguished from HeFH. Thorough family studies and genetic analysis are recommended for their accurate diagnosis.Fatal cardiovascular complications could develop even in the first decade of life for HoFH, so aggressive lipid-lowering therapy should be initiated as early as possible. Direct removal of plasma LDL by lipoprotein apheresis has been the principal measure for these patients. However, this treatment alone may not achieve stable LDL-C target levels and combination with drugs should be considered. The lipid-lowering effects of statins and PCSK9 inhibitors substantially vary depending on the remaining LDL receptor activity of individual patients. On the other hand, the action an MTP inhibitor is independent of LDL receptor activity, and it is effective in most HoFH cases.This review summarizes the key clinical issues of HoFH as well as insurance coverage available under the Japanese public healthcare system.
Statement1. Familial hypercholesterolemia (FH) is an autosomal hereditary disease with the 3 major clinical features of hyper-LDL-cholesterolemia, premature coronary artery disease and tendon and ...skin xanthomas. As there is a considerably high risk of coronary artery disease (CAD), in addition to early diagnosis and intensive treatment, family screening (cascade screening) is required (Recommendation level A) 2. For a diagnosis of FH, at least 2 of the following criteria should be satisfied:① LDL-C ≥180 mg/dL, ② Tendon/skin xanthomas, ③ History of FH or premature CAD within 2nd degree blood relatives (Recommendation level A) 3. Intensive lipid-lowering therapy is necessary for the treatment of FH. First-line drug should be statins. (Recommendation level A, Evidence level 3) 4. Screening for CAD as well as asymptomatic atherosclerosis should be conducted periodically in FH patients. (Recommendation level A) 5. For homozygous FH, consider LDL apheresis and treatment with PCSK9 inhibitors or MTP inhibitors. (Recommendation level A) 6. For severe forms of heterozygous FH who have resistant to drug therapy, consider PCSK9 inhibitors and LDL apheresis. (Recommendation level A) 7. Refer FH homozygotes as well as heterozygotes who are resistant to drug therapy, who are children or are pregnant or have the desire to bear children to a specialist. (Recommendation level A)
This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in ...order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be ＜140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.
Preamble Every 5 years, the JAS publishes guidelines for the treatment of dyslipidemia and atherosclerosis. To date, this society has released four such guidelines. Since 2007, the JAS has included ...objectives that consider all the risk factors for atherosclerotic cardiovascular diseases (ASCVD) and has accordingly been publishing manuals, such as the "Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases." Because guidelines should be based on evidence of diagnoses and treatments that have already been validated, regular revisions are necessary to administer medical care of high quality. Apart from age, gender, and family history, for which clinical intervention is not possible, the major risk factors for ASCVD include diabetes, hypertension, smoking, and dyslipidemia. Dyslipidemia is a huge risk factor for coronary artery disease (CAD), a form of ASCVD, and in the current set of guidelines, we will be dealing with CAD as the main disease of interest. Nevertheless, other risk factors also ought to be thoroughly managed as part of the efforts for preventing ASCVD. In 1987, a consensus conference on hyperlipidemia was held at the JAS, and reference values for diagnosing hyperlipidemia were proposed.
Diagnosis and Management of Sitosterolemia 2021 Tada, Hayato; Nomura, Akihiro; Ogura, Masatsune ...
Journal of Atherosclerosis and Thrombosis,
2021-Aug-01, Letnik:
28, Številka:
8
Journal Article
Odprti dostop
Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in ATP-binding ...cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in selective excretion of plant sterols from the liver and intestine, leading to failure to prevent absorption of food plant sterols. This disorder has been considered to be extremely rare. However, accumulated clinical data as well as genetics suggest the possibility of a much higher prevalence. Its clinical manifestations resemble those observed in patients with familial hypercholesterolemia (FH), including tendon xanthomas, hyper LDL-cholesterolemia, and premature coronary atherosclerosis. We provide an overview of this recessive genetic disease, diagnostic as well as therapeutic tips, and the latest diagnostic criteria in Japan.
Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This ...study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan.Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals.Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL.Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.
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