Risk factors for low high-density lipoprotein among Asian Indians in the United States.
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ABSTRACT:
SUBMITTER: Lucke-Wold B
PROVIDER: S-EPMC5483428 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
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Project description:The LDL receptor (LDLR) and scavenger receptor class B type I (SR-BI) play physiological roles in LDL and HDL metabolism in vivo. In this study, we explored HDL metabolism in LDLR-deficient mice in comparison with WT littermates. Murine HDL was radiolabeled in the protein ((125)I) and in the cholesteryl ester (CE) moiety ([(3)H]). The metabolism of (125)I-/[(3)H]HDL was investigated in plasma and in tissues of mice and in murine hepatocytes. In WT mice, liver and adrenals selectively take up HDL-associated CE ([(3)H]). In contrast, in LDLR(-/-) mice, selective HDL CE uptake is significantly reduced in liver and adrenals. In hepatocytes isolated from LDLR(-/-) mice, selective HDL CE uptake is substantially diminished compared with WT liver cells. Hepatic and adrenal protein expression of lipoprotein receptors SR-BI, cluster of differentiation 36 (CD36), and LDL receptor-related protein 1 (LRP1) was analyzed by immunoblots. The respective protein levels were identical both in hepatic and adrenal membranes prepared from WT or from LDLR(-/-) mice. In summary, an LDLR deficiency substantially decreases selective HDL CE uptake by liver and adrenals. This decrease is independent from regulation of receptor proteins like SR-BI, CD36, and LRP1. Thus, LDLR expression has a substantial impact on both HDL and LDL metabolism in mice.
| S-EPMC4617360 | biostudies-literature
Project description:BackgroundPrevious studies have demonstrated gaps in achievement of low-density lipoprotein-cholesterol (LDL-C) goals among U.S. individuals at high cardiovascular disease risk; however, recent studies in selected populations indicate improvements.ObjectiveWe sought to define the longitudinal trends in achieving LDL-C goals among high-risk United States adults from 1999-2008.MethodsWe analyzed five sequential population-based cross-sectional National Health and Nutrition Examination Surveys 1999-2008, which included 18,656 participants aged 20-79 years. We calculated rates of LDL-C goal achievement and treatment in the high-risk population.ResultsThe prevalence of high-risk individuals increased from 13% to 15.5% (p?=?0.046). Achievement of LDL-C <100 mg/dL increased from 24% to 50.4% (p<0.0001) in the high-risk population with similar findings in subgroups with (27% to 64.8% p<0.0001) and without (21.8% to 43.7%, p<0.0001) coronary heart disease (CHD). Achievement of LDL-C <70 mg/dL improved from 2.4% to 17% (p<0.0001) in high-risk individuals and subgroups with (3.4% to 21.4%, p<0.0001) and without (1.7% to 14.9%, p<0.0001) CHD. The proportion with LDL-C ?130 mg/dL and not on lipid medications decreased from 29.4% to 18% (p?=?0.0002), with similar findings among CHD (25% to 11.9% p?=?0.0013) and non-CHD (35.8% to 20.8% p<0.0001) subgroups.ConclusionThe proportions of the U.S. high-risk population achieving LDL-C <100 mg/dL and <70 mg/dL increased over the last decade. With 65% of the CHD subpopulation achieving an LDL-C <100 mg/dL in the most recent survey, U.S. LDL-C goal achievement exceeds previous reports and approximates rates achieved in highly selected patient cohorts.
| S-EPMC3615020 | biostudies-literature
Project description:BackgroundRecent studies, primarily in non-Hispanic whites, suggest that dietary patterns have distinct metabolomic signatures that may influence disease risk. However, evidence in South Asians, a group with unique dietary patterns and a high prevalence of cardiometabolic risk, is lacking.ObjectiveWe investigated the metabolomic profiles associated with 2 distinct dietary patterns among a sample of Asian Indians living in the United States. We also examined the cross-sectional associations between metabolomic profiles and cardiometabolic risk markers.MethodsWe used cross-sectional data from 145 Asian Indians, aged 45-79 y, in the Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) pilot study. Metabolomic profiles were measured from fasting serum samples. Usual diet was assessed by using a validated food-frequency questionnaire. We used principal components analysis to derive dietary and metabolomic patterns. We used adjusted general linear regression models to examine associations between dietary patterns, individual food groups, metabolite patterns, and cardiometabolic risk markers.ResultsWe observed 2 major principal components or metabolite clusters, the first comprised primarily of medium- to long-chain acylcarnitines (metabolite pattern 1) and the second characterized by branched-chain amino acids, aromatic amino acids, and short-chain acylcarnitines (metabolite pattern 2). A "Western/nonvegetarian" pattern was significantly and positively associated with metabolite pattern 2 (all participants: ? ± SE = 0.180 ± 0.090, P = 0.05; participants without type 2 diabetes: ? ± SE = 0.323 ± 0.090, P = 0.0005). In all participants, higher scores on metabolite pattern 2 were adversely associated with measures of glycemia (fasting insulin: ? ± SE = 2.91 ± 1.29, P = 0.03; 2-h insulin: ? ± SE = 22.1 ± 10.3, P = 0.03; homeostasis model assessment of insulin resistance: ? ± SE = 0.94 ± 0.42, P = 0.03), total adiponectin (? ± SE = -1.46 ± 0.47, P = 0.002), lipids (total cholesterol: ? ± SE = 7.51 ± 3.45, P = 0.03; triglycerides: ? ± SE = 14.4 ± 6.67, P = 0.03), and a radiographic measure of hepatic fat (liver-to-spleen attenuation ratio: ? ± SE = -0.83 ± 0.42, P = 0.05).ConclusionsOur findings suggest that a "Western/nonvegetarian" dietary pattern is associated with a metabolomic profile that is related to an adverse cardiometabolic profile in Asian Indians. Public health efforts to reduce cardiometabolic disease burden in this high-risk group should focus on consuming a healthy plant-based diet.
| S-EPMC6251517 | biostudies-literature
Project description:Marked increases in the awareness, treatment, and control of high low-density lipoprotein (LDL) cholesterol occurred among United States (US) adults from 1988-1994 to 1999-2004. An update to the Third Adult Treatment Panel guidelines was published in 2004, and it is unknown if these improvements have continued since the publication of these revised treatment recommendations. The aim of this study was to determine trends in the awareness, treatment, and control of high LDL cholesterol among US adults from 1999-2000 to 2009-2010 using nationally representative samples of US adults aged ?20 years from 6 consecutive National Health and Nutrition Examination Surveys (NHANES) in 1999-2000 (n = 1,659), 2001-2002 (n = 1,897), 2003-2004 (n = 1,698), 2005-2006 (n = 1,692), 2007-2008 (n = 2,044), and 2009-2010 (n = 2,318). LDL cholesterol was measured after an overnight fast, and high LDL cholesterol and controlled LDL cholesterol were defined using the 2004 updated Third Adult Treatment Panel guidelines. Awareness and treatment of high cholesterol were defined using self-report. Among US adults, the prevalence of high LDL cholesterol did not change from 1999-2000 (37.2%) to 2009-2010 (37.8%). Awareness of high LDL cholesterol increased from 48.9% in 1999-2000 to 62.8% in 2003-2004 but did not increase further through 2009-2010 (61.5%). Among those aware of having high LDL cholesterol, treatment increased from 41.3% in 1999-2000 to 72.6% in 2007-2008 and was 70.0% in 2009-2010. Among US adults receiving treatment for high LDL cholesterol, the percentage with controlled LDL cholesterol increased from 45.0% in 1999-2000 to 65.3% in 2005-2006 and had decreased slightly by 2009-2010 (63.6%). In conclusion, high LDL cholesterol remains common among US adults. Additional efforts are needed to prevent high LDL cholesterol and increase the awareness, treatment, and control of high LDL cholesterol among US adults.
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Project description:BackgroundEnlargement of adipocyte is associated with their dysfunction and alterations in metabolic functions.ObjectivesWe evaluated the association of adipocyte size of subcutaneous and omental adipose tissue with body composition and cardiovascular risk factors in Asian Indians.MethodologyEighty (40 males and 40 females) non-diabetic adult subjects undergoing elective abdominal surgery were included. Pre-surgery evaluation included anthropometric measurements, % body fat by bioimpedance, abdominal fat area at L2-3 level (computed tomography) and biochemical investigations (fasting blood glucose and insulin, lipids and hsCRP). During surgery, about 5 grams each of omental and subcutaneous adipose tissue was obtained for adipocyte size determination.ResultsFemales had higher BMI, % body fat, skinfold thickness, total and subcutaneous abdominal fat area as compared to males. Overweight was present in 42.5% and 67.5%, and abdominal obesity in 5% and 52.5% males and females, respectively. Subcutaneous adipocyte size was significantly higher than omental adipocyte size. Omental adipocyte size correlated more strongly than subcutaneous adipocyte size with measures of adiposity (BMI, waist circumference, %BF), total and subcutaneous abdominal fat area and biochemical measures (fasting glucose, total cholesterol, triglycerides and HOMA-IR), the correlations being stronger in females. The correlation of adipocyte size with metabolic parameters was attenuated after adjusting for measures of adiposity.ConclusionOmental adipocyte size, though smaller than the subcutaneous adipocyte size, was more closely related to measures of adiposity and metabolic parameters. However, the relationship was not independent of measures of adiposity.
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Project description:Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface. Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence of interfacial tension becomes significant for particles with a radius of ?5 nm, when the area per molecule in the surface region is <1.4 nm(2). Further, interfacial tensions in the used HDL and LDL models are essentially unaffected by single apo-proteins at the surface. Finally, interfacial tensions of lipoproteins are higher than in thermodynamically stable droplets, suggesting that HDL and LDL are kinetically trapped into a metastable state.
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Project description:Objective The triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is related to insulin resistance (IR). However, information about whether or not the TG/HDL-C ratio is associated with low-density lipoprotein (LDL) subclasses in the Japanese population is limited. Methods In total, 1,068 Japanese subjects who underwent an annual health examination and who were not taking medications were recruited. The association between the TG/HDL-C ratio and LDL subclasses was investigated using correlation, multiple regression, and receiver operating characteristic analyses. Results A correlation analysis revealed that both malondialdehyde-modified low-density lipoprotein (MDA-LDL) and small dense low-density lipoprotein cholesterol (sdLDL-C) were positively associated with the TG/HDL-C ratio. Furthermore, a multiple linear regression analysis revealed that the TG/HDL-C ratio was positively associated with MDA-LDL and sdLDL-C in both men and women. The multiple logistic regression analysis also revealed that the TG/HDL-C ratio was positively associated with the upper tertile of MDA-LDL and sdLDL-C in men and women. The LDL-C levels increased with the increasing TG/HDL-C ratio. The MDA-LDL and sdLDL-C are known to be positively associated with LDL-C. However, within the same LDL-C range, both MDA-LDL and sdLDL-C levels increased with the TG/HDL-C ratio, except for MDA-LDL levels in the LDL-C <112 mg/dL group in women. These results further supported the notion that the TG/HDL-C ratio was positively associated with the MDA-LDL and sdLDL-C levels, especially in the higher LDL-C range, in both men and women. The optimal cut-off points of the TG/HDL-C ratio for the upper tertile of MDA-LDL and sdLDL-C were 1.85 and 2.03 in men and 0.88 and 1.30 in women, respectively. Conclusion The TG/HDL-C ratio is positively associated with MDA-LDL and sdLDL-C in Japanese subjects. The relationship was particularly notable in subjects with high LDL-C levels.
| S-EPMC7691041 | biostudies-literature
Project description:CONTEXT:Elevated LDL cholesterol (LDL-C) is an important risk factor for atherosclerosis and cardiovascular disease. Variants in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have been associated not only with plasma LDL-C concentration, but also with ischemic heart disease. Little is known about the genetic architecture of PCSK9 and its influence on LDL-C in American Indians. OBJECTIVE:We aimed to investigate the genetic architecture in the 1p32 region encompassing PCSK9 and its influence on LDL-C in American Indians. DESIGN:The Strong Heart Family Study (SHFS) is a family-based genetic study. PARTICIPANTS:Two thousand four hundred fifty eight American Indians from Arizona, Oklahoma, North Dakota, and South Dakota, who were genotyped by Illumina MetaboChip. RESULTS:We genotyped 486 SNPs in a 3.9 Mb region at chromosome 1p32 encompassing PCSK9 in 2458 American Indians. We examined the association between these SNPs and LDL-C. For common variants (MAF ? 1%), meta-analysis across the three geographic regions showed common variants in PCSK9 were significantly associated with higher LDL-C. The most significant SNP rs12067569 (MAF = 1.7 %, ? = 16.9 ± 3.7, P = 5.9 × 10(-6)) was in complete LD (r(2) = 1) with a nearby missense SNP, rs505151 (E670G) (? = 15.0 ± 3.6, P = 3.6 × 10(-5)). For rare variants (MAF < 1%), rs11591147 (R46L, MAF = 0.9%) was associated with lower LDL-C (? = - 31.1 ± 7.1, P = 1.4 × 10(-5)). The mean (SD) of LDL-C was 76.9 (7.8) and 107.4 (1.0) mg/dL for those with and without the R46L mutation, respectively. One person who was homozygous for R46L had LDL-C levels of 11 mg/dL. In one family, 6 out of 8 members carrying the R46L mutation had LDL-C levels below the lower 10% percentile of LDL-C among all study participants. CONCLUSIONS:Both rare and common variants in PCSK9 influence plasma LDL-C levels in American Indians. Follow-up studies may disclose the influence of these mutations on the risk of CVD and responses to cholesterol-lowering medications.
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Project description:ObjectiveThe Asian American population in the U.S. comprises various, ethnically diverse subgroups. Traditionally, this population has been studied as a single, aggregated group, potentially masking differences in risk among subgroups. Analyses using disaggregated data can help better characterize the health needs of different Asian subpopulations and inform targeted, effective public health interventions. We assessed the prevalence of cardiovascular disease (CVD) risk factors and atherosclerotic CVD (ASCVD) and their associations with socioeconomic factors among Chinese, Asian Indian, Filipino and Other Asian subjects, compared with non-Hispanic White (NHW) subjects in the U.S.Methods: Cross-sectional study using data from 298,286 adults from the National Health Interview Survey (NHIS) from 2007 to 2018. We utilized chi-squared tests to compare characteristics across subgroups. Weighted proportions and unadjusted and adjusted logistic regression models were utilized to examine the associations between Asian subgroups, self-reported CVD risk factors and self-reported ASCVD, as well as between socioeconomic factors within each Asian subgroup.Results: Asian Indian subjects had the highest prevalence of diabetes (12.5%), while Filipino subjects had the highest prevalence of hyperlipidemia (27.7%), hypertension (29.8%) and obesity (19.8%). Despite this, the prevalence of self-reported ASCVD was lower in all Asian groups compared with NHWs. Chinese subjects had the lowest odds of having each of the CVD risk factors assessed.Conclusion: We found considerable heterogeneity in the distribution of risk factors as well as ASCVD among Asian subgroups in the US. Compared with health system or community-based reports, the prevalence of risk factors and ASCVD may be underestimated in some Asian NHIS subgroups. There is an urgent need for efforts to improve recruitment of Asian participants of heterogeneous socioeconomic backgrounds in national surveys, as well as to perform a thorough assessment of risk factors and disease in this population, not relying solely on self-report.
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