The term “lipid triad” or “atherogenic lipoprotein phenotype” has been introduced to describe a common form of dyslipidemia, characterized by three lipid abnormalities: increased plasma triglyceride levels, decreased HDL-cholesterol concentrations and the presence of small, dense LDL particles. It has been suggested that the clinical importance of the atherogenic lipoprotein phenotype probably exceeds that of LDL-cholesterol, because many more patients with coronary artery disease are found to have this trait than hypercholesterolaemia. There is a body of evidence that therapies effective against plasma HDL-cholesterol and triglycerides are associated with a strong reduction of cardiovascular risk; in addition, hypolipidemic treatment is able to increase LDL particle size and this increment correlates with regression of coronary stenosis. Recently, the Coordinating Committee of the National Cholesterol Education Program suggested that very high-risk patients may benefit from stronger lipid-lowering measures, a category of individuals that includes those with the atherogenic lipoprotein phenotype. Since the therapeutical modulation of each of the three components of the lipid triad is associated with a strong reduction in the risk of cardiovascular events, LDL size measurement may be extended as much as possible to patients at high risk of cardiovascular diseases.

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We studied the association of six common polymorphisms of four genes related to lipid metabolism with serum lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the genes for cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (LIPC), and apolipoprotein CIII (APOC3), and studied 2267 individuals randomly selected from the participants of Serum Lipid Survey 2000. There was a significant association of CETP polymorphism (D442G, Int14 +1 G → A, and TaqIB), LPL polymorphism (S447X), and LIPC polymorphism (−514 → CT) with HDL-cholesterol levels. We also found a significant association of LPL polymorphism (S447X) and APOC3 polymorphism (SstI) with triglyceride levels. This is the largest database showing the association of common genetic variants in lipid metabolism with serum lipid levels in the general Japanese population. Further study is necessary to elucidate the role of these gene polymorphisms in cardiovascular events.

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The role of lipids, lipoproteins and lipoprotein(a) [Lp(a)] in coronary artery disease (CAD) is known but the role of major apolipoproteins (apos) other than apo A-I and apo B remains unclear. In this study, using immunoturbidimetry we have estimated serum levels of total cholesterol, HDL-C, LDL-C, triglyceride, LDL-apoB and all major apos; A-I, A-II, B, C-II, C-III and E, in 751 healthy Indian subjects (470 men and 281 women, age 25−65 years), determined their percentiles, and established reference intervals. The effects of age, smoking and alcohol on all these analytes were also evaluated. This is the first study to provide reference intervals for all apos, in both sexes from a general population. The percentiles and the reference intervals have clinical relevance and will be useful in assessing the risk of CAD in patients with hyperlipidemia and other diseases.

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This study was performed to investigate whether the plasma concentration of phosphatidylcholine hydroperoxide (PCOOH), which is a marker of oxidized stress in the blood, increased in cholesterol-fed rabbits, and fructose ingestion promoted this process and aggravated atherosclerosis. Male Japanese white rabbits (age: 12 weeks, and body weight: around 2.0 kg, n = 15) were divided into three groups, (1) a NN group as a normal control fed a standard diet (n = 5), (2) a CN group fed 1.0% cholesterol, and (3) a CF group given both 1.0% cholesterol and 10% fructose-containing tap water. During 8 weeks, plasma PCOOH levels increased significantly in the CN and CF groups compared to the NN group and fructose further raised the PCOOH level. The atherosclerosis was significantly promoted and the deposition of advanced glycation end products (AGEs) was marked in the CF group compared to the CN group. Fructose worsened the atheromatous lesions caused by cholesterol feeding. The mechanism is most likely through lipid peroxidation, which was increased by cholesterol feeding-induced hyperlipidemia, and the formation of AGEs.

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It is not known whether subjects with metabolic syndrome and elevated blood pressure are at the same cardiovascular risk as subjects with metabolic syndrome but without elevated blood pressure. Using B-mode ultrasonography, carotid IMT was measured in 1,297 patients (593 men and 704 women) in the medical department of Seiyo Municipal Nomura Hospital between August 1996 and April 2005. The prevalence of metabolic syndrome was 32.5% among men and 35.9% among women. On comparing subjects with an equal number of components of metabolic syndrome, it was found that the prevalence of carotid atherosclerosis was significantly higher in subjects with elevated blood pressure than in those without, and increased with the number of components in the former group (p for trend = 0.0277), but not in the latter (p for trend = 0.5159). In a stepwise multiple logistic regression analysis, after adjustment for confounding factors, elevated blood pressure (OR, 1.771; 95% CI, 1.246−2.519), low HDL-C (OR, 1.391; 95% CI, 1.053−1.836) and number of components of metabolic syndrome (OR, 1.561; 95% CI, 1.103−2.209) were significantly associated with carotid atherosclerosis. The diagnosis of metabolic syndrome per se might not adequately identify subjects at increased cardiovascular risk.

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Background: Familial Hypercholesterolemia (FH) is an autosomal dominant disease resulting from mutations of the LDL (LDLR) receptor gene leading to a diminished catabolism and elevated level of LDL cholesterol (LDL-C). It is associated with an increased risk for cardiovascular disease (CVD). The MEDPED (Make Early Diagnosis-Prevent Early Death) program, an initiative cited by the WHO Human Genetics Programme in their report on FH, initiated international collaboration to identify and follow-up patients with FH globally. From Asia-Pacific, only 6 countries are participating and no data among Filipinos particularly on genetic profiles is available at present. This study attempts to initiate data collection and participation in the global initiative.
Objectives:
Primary: 1. To describe the phenotype of Filipino patients with FH.
2. To determine and characterize the LDL-R gene mutations among Filipino patients with clinical features of FH
Secondary: To determine the association of the clinical characteristics of FH with the presence of LDLR gene mutations
Design: Cross- Sectional Study
Setting: Multicenter, Outpatient Clinic
Participants: 60 unrelated patients, 18 y/o and above from UP-PGH, Manila Doctors Hospital and Cardinal Santos Medical Center. FH was dignosed according to the Dutch Lipid Clinic Network Criteria cited by WHO which is based on a history of premature CVD, family history, tendon xanthoma, arcus cornealis, and LDL C levels.
Methods: With informed consent, clinical history, physical examination and lipid profile data were determined. Blood samples were extracted, processed to isolate DNA specimens at the National Institutes of Health, Institute of Human Genetics, and sent to Canterbury Health Laboratories at Christchurch, New Zealand for DNA analysis.
Analysis: Descriptive statistics, Fisher’s exact test and Student’s t-test using Stata version 6.0 software.
Results: Sixty patients with a mean age of 55 y/o were included, including 39 (65%) females. The mean LDL level was 227 mg/dl. Cardiovascular Disease and a family history of dyslipidemia were present in 55 & 60% of the samples, respectively. Twenty percent had documented LDL-R gene mutations. Six of the mutations were considered novel. A family history of dyslipidemia, an elevated LDL-C level, and a high FH score exhibited a statistically significant association with mutations.
Conclusion: The study population has a high prevalence of CVD at an average age of 55 years with a strong family history of dyslipidemia and very high average LDL-C levels. One out of every 5 patients had LDL-R gene mutations, 6 of which were considered novel. LDL-R gene mutation was significantly associated with family history of dyslipidemia, LDL-C Level and FH score.
Clinical and Research Implication: This is the first international collaborative genetic study among Filipinos with FH. Data could allow the country to participate in the WHO/MEDPED global program. Collaborative efforts will lead to more effective detection, treatment and prevention of CV events. Novel mutations were discovered and further analysis of these genes will be done.

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We determined the prevalence of metabolic syndrome (MS) in Okinawa from cross-sectional results of an annual physical chekup. We also calculated the homeostasis model assessment ratio (HOMA-R) as an index of insulin resistance, and examined the relationship between HOMA-R and MS. We studied 3,839 men (mean age 49.2 years) and 3,146 women (mean age 50.0 years), a total of 6,985 people aged from 30 to 79 years, who underwent an annual physical chekup in our hospital between May 2003 and March 2004. The diagnosis of MS was based on the criteria in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III: ATP III). Abdominal circumference was assessed in accordance with the diagnostic criteria of the Japan Society for the Study of Obesity. The prevalence of MS was 30.2% in men and 10.3% in women. Mean HOMA-R significantly increased with an increase in the number of ATP III risk factors. Logistic regression analysis with the independent variables of sex, age, and HOMA-R gave an odds ratio of MS of 3.6 for men, 1.4 for a 10-year age increment, and 2.0 for an elevation of HOMA-R above 1.0.

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Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by a high level of LDL-cholesterol and frequent coronary atherosclerosis. We studied a 64 year old woman with heterozygous (hetero) FH, who showed symptoms of chest pain and dyspnea with no other coronary risk factors than post-menopause and hypercholesterolemia. Although her coronary symptoms didn’t reveal significant stenosis on coronary angiography, she had severe aortic valvular and supravalvular stenosis at the ascending aorta, which qualified her for aortic valve replacement. Moreover, a coronary flow study revealed functional ischemia with a reduction of the coronary flow reserve. We report a case of valvular and supravalvular aortic stenosis corrected by aortic valve replacement, a rare complication of hetero FH.

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