Characterizing genetic profiles for high triglyceride levels in U.S. patients of African ancestry.

Hypertriglyceridemia (HTG) is a common cardiovascular risk factor characterized by elevated triglyceride (TG) levels. Researchers have assessed the genetic factors that influence HTG in studies focused predominantly on individuals of European ancestry. However, relatively little is known about the contribution of genetic variation of HTG in people of African ancestry (AA), potentially constraining research and treatment opportunities. Our objective was to characterize genetic profiles among individuals of AA with mild-to-moderate HTG and severe HTG versus those with normal TGs by leveraging whole-genome sequencing data and longitudinal electronic health records available in the All of Us program. We compared the enrichment of functional variants within five canonical TG metabolism genes, an AA-specific polygenic risk score for TGs, and frequencies of 145 known potentially causal TG variants between HTG patients and normal TG among a cohort of AA patients (N = 15,373). Those with mild-to-moderate HTG (N = 342) and severe HTG (N ≤ 20) were more likely to carry APOA5 p.S19W (odds ratio = 1.94, 95% confidence interval = [1.48-2.54], P = 1.63 × 10-6 and OR = 3.65, 95% confidence interval: [1.22-10.93], P = 0.02, respectively) than those with normal TG. They were also more likely to have an elevated (top 10%) polygenic risk score, elevated carriage of potentially causal variant alleles, and carry any genetic risk factor. Alternative definitions of HTG yielded comparable results. In conclusion, individuals of AA with HTG were enriched for genetic risk factors compared to individuals with normal TGs.

Association of MARC1, ADCY5, and BCO1 Variants with the Lipid Profile, Suggests an Additive Effect for Hypertriglyceridemia in Mexican Adult Men.

Epidemiological studies have reported that the Mexican population is highly susceptible to dyslipidemia. The MARC1, ADCY5, and BCO1 genes have recently been involved in lipidic abnormalities. This study aimed to analyze the association of single nucleotide polymorphisms (SNPs) rs2642438, rs56371916, and rs6564851 on MARC1, ADCY5, and BCO1 genes, respectively, with the lipid profile in a cohort of Mexican adults. We included 1900 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. A genetic risk score (GRS) was created on the basis of the three genetic variants. Associations analysis was estimated using linear and logistic regression. Our results showed that rs2642438-A and rs6564851-A alleles had a risk association for hypertriglyceridemia (OR = 1.57, p = 0.013; and OR = 1.33, p = 0.031, respectively), and rs56371916-C allele a trend for low HDL-c (OR = 1.27, p = 0.060) only in men. The GRS revealed a significant association for hypertriglyceridemia (OR = 2.23, p = 0.022). These findings provide evidence of an aggregate effect of the MARC1, ADCY5, and BCO1 variants on the risk of hypertriglyceridemia in Mexican men. This knowledge could represent a tool for identifying at-risk males who might benefit from early interventions and avoid secondary metabolic traits.

Determination of optimal cut-off points after a high-fat meal corresponding to fasting elevations of triglyceride and remnant cholesterol in Chinese subjects.

BACKGROUND: Postprandial high triglyceride (HTG), marking elevated level of remnant cholesterol (RC), is an independent risk factor of coronary heart disease (CHD). The postprandial cut-off points for HTG and high RC (HRC) after a daily meal are recommended as 2.0 mmol/L and 0.9 mmol/L, respectively, by the European Atherosclerosis Society (EAS), while those after a high-fat meal in Chinese subjects were not explored. METHODS: Ninety subjects, including 60 CHD patients (CHD group) and 30 non-CHD controls (CON group), were enrolled in this study. Serum levels of blood lipids, including calculated RC, were monitored at 0, 2, 4 and 6 h after a high-fat meal with 800 kcal and 50 g fat. Analysis of c-statistic was used to determine the cut-off points for postprandial HTG and HRC. RESULTS: Postprandial levels of triglyceride (TG) and RC significantly increased and peaked at 4 h after a high-fat meal in two groups, although those in CHD group were significantly higher (P < 0.05). The optimal cut-off point to predict HTG at 4 h corresponding to fasting TG ≥ 1.7 mmol/L was 3.12 mmol/L, and that to predict HRC at 4 h corresponding to fasting RC ≥ 0.8 mmol/L was 1.36 mmol/L. According to the new cut-off points, the omissive diagnosis rates of postprandial HTG and HRC decreased obviously. CONCLUSION: The cut-off points of postprandial HTG and HRC in Chinese subjects after a high-fat meal were higher than those after a daily meal recommended by the EAS, indicating that specific cut-off points should be determined after a certain high-fat meal.

[Prevalence of diabetes and its associated factors in Blang ethnic adults].

Objective: To investigate the prevalence and associated risk factors of diabetes and prediabetes in Blang ethnic adults in Menghai county. Methods: A cross-sectional survey including 3 365 Blang ethnic adults (aged 18 and above from 5 administrative villages) was conducted from February 2017 to March 2017 in Menghai county. A questionnaire, physical examination, and blood assays were included in the survey. Finally, a total of 3 237 adults with complete data were selected into this analysis. Results: The standardized prevalence of diabetes and prediabetes in Blang ethnic adults were estimated based on the sixth national census in 2010. According to the 1999 WHO criteria, the overall standardized prevalence of diabetes and prediabetes were 8.5% (men: 10.2%, women: 6.8%) and 16.1% (men: 18.0%, women: 14.1%), in which the standardized prevalence of newly diagnosed diabetes among the total population was 7.3% (men: 8.7%, women: 5.8%). Multivariable multinominal logistic regression analyses showed that age, hypertension, hypertriglyceridemia, and central obesity were significantly positively associated with both diabetes and prediabetes, with the corresponding odds ratios of 1.74 and 1.37, 2.39 and 2.02, 2.30 and 1.34, 2.55 and 1.73, respectively. Conclusion: The prevalence of diabetes is relatively high in Blang ethnic adults in Menghai county. Improving knowledge of diabetes among the local population is one of key steps in the prevention of diabetes.

Triglyceride-rich very low-density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents.

Excess insulin secretion and hyperinsulinaemia contribute to the progression of type 2 diabetes. However, the mechanisms leading to insulin hypersecretion remain largely unknown. Based on our preliminary data, we examined whether triglycerides and very low-density lipoprotein (VLDL) are independently associated with insulin secretion, and whether ethnicity/race modulates these associations. Fasting triglycerides and VLDL were measured in a multiethnic cohort of 630 non-diabetic adolescents. Insulin secretion, ß-cell function parameters, insulin sensitivity and insulin clearance were estimated through a 3-h oral glucose tolerance test. Metabolic assessments were repeated after 2 years in 239 subjects. Triglycerides and triglyceride-rich VLDL (large and medium size fractions) were associated with both basal and glucose-stimulated insulin secretion, after adjustment for age, sex, ethnicity, BMI z-score, plasma glucose, and insulin sensitivity. Ethnicity per se had an impact on lipid profile and ß-cell function, but did not modulate the effect of triglycerides/VLDL on insulin secretion. At follow-up, changes in triglyceride levels were proportional to changes in insulin secretion. These findings support the hypothesis that hypertriglyceridaemia is an important stimulus for ß-cell insulin release in young people under both fasting and fed conditions.

[Prevalence and risk factors of diabetes and prediabetes in adults in Jingyuan Ningxia].

Objective: To investigate the prevalence and risk factors of diabetes and prediabetes in Jingyuan County in Ningxia. Methods: A cross-sectional survey including 10 639 participants (18-88 years of age) with a multistage sampling was conducted in Jingyuan County between January, 2014 and April, 2015. Questionnaires, physical examinations, and laboratory tests were included in the survey. Results: Among all the subjects, 10 491 participants (men: 4 826, women: 5 665) with complete data were included in the analysis. The standardized prevalence of diabetes and prediabetes was 4.2% (men: 3.9%, women: 4.5%) and 8.8% (men: 7.6%, women 10.3%), respectively, in which the standardized prevalence of diabetes was higher in Hui (4.5%) than that in Han (3.5%) (P< 0.05). Logistic regression analyses showed that age, family history of diabetes, overweight/obesity, hypertriglyceridemia and hypertension were positively associated with prediabetes and diabetes with the odds ratios being 1.60 and 2.14 (age, P< 0.001), 1.40 and 3.32 (family history, P< 0.05), 1.47 and 1.57 (overweight/obesity, P< 0.001), 1.88 and 2.55 (hypertriglyceridemia, P< 0.001), 1.44 and 1.89 (hypertension, P< 0.001), respectively. Conclusions: The prevalence of diabetes was relatively low in the rural area in Ningxia. However, it is still essential to take active interventions in people at high risk of diabetes in order to prevent the incident diabetes.

Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.

BACKGROUND: Women with polycystic ovarian syndrome have a high prevalence of metabolic syndrome and type 2 diabetes mellitus. Blacks and Hispanics have a high morbidity and mortality due to cardiovascular disease and diabetes mellitus in the general population. Since metabolic syndrome is a risk factor for development of type 2 diabetes and cardiovascular disease, understanding any racial and ethnic differences in metabolic syndrome among women with polycystic ovarian syndrome is important for prevention strategies. However, data regarding racial/ethnic differences in metabolic phenotype among women with polycystic ovary syndrome are inconsistent. OBJECTIVE: We sought to determine if there are racial/ethnic differences in insulin resistance, metabolic syndrome, and hyperandrogenemia in women with polycystic ovarian syndrome. STUDY DESIGN: We conducted secondary data analysis of a prospective multicenter, double-blind controlled clinical trial, the Pregnancy in Polycystic Ovary Syndrome II study, conducted in 11 academic health centers. Data on 702 women with polycystic ovarian syndrome aged 18-40 years who met modified Rotterdam criteria for the syndrome and wished to conceive were included in the study. Women were grouped into racial/ethnic categories: non-Hispanic whites, non-Hispanic blacks, and Hispanic. The main outcomes were the prevalence of insulin resistance, metabolic syndrome, and hyperandrogenemia in the different racial/ethnic groups. RESULTS: Body mass index (35.1 ± 9.8 vs 35.7 ± 7.9 vs 36.4 ± 7.9 kg/m2) and waist circumference (106.5 ± 21.6 vs 104.9 ± 16.4 vs 108.7 ± 7.3 cm) did not differ significantly between non-Hispanic white, non-Hispanic black, and Hispanic women. Hispanic women with polycystic ovarian syndrome had a significantly higher prevalence of hirsutism (93.8% vs 86.8%), abnormal free androgen index (75.8% vs 56.5%), abnormal homeostasis model assessment (52.3% vs 38.4%), and hyperglycemia (14.8% vs 6.5%), as well as lower sex hormone binding globulin compared to non-Hispanic whites. Non-Hispanic black women had a significantly lower prevalence of metabolic syndrome (24.5% vs 42.2%) compared with Hispanic women, and lower serum triglyceride levels compared to both Hispanics and non-Hispanic whites (85.7 ± 37.3 vs 130.2 ± 57.0 vs 120.1 ± 60.5 mg/dL, P < .01), with a markedly lower prevalence of hypertriglyceridemia (5.1% vs 28.3% vs 30.5%, P < .01) compared to the other 2 groups. CONCLUSION: Hispanic women with polycystic ovarian syndrome have the most severe phenotype, both in terms of hyperandrogenism and metabolic criteria. Non-Hispanic black women have an overall milder polycystic ovarian syndrome phenotype than Hispanics and in some respects, than non-Hispanic white women.

Prevalence of Selected Intermediate Risk Factors for Non-communicable Diseases in an Apparently Healthy Indian Community in KwaZulu-Natal, South Africa.

South Africa, burdened with the emerging chronic diseases, is home to one of the largest migrant Indian population, however, little data exists on the risk factors for non-communicable diseases in this population. The aim of this study was to determine the prevalence of yet undiagnosed selected intermediate risk factors for non-communicable diseases among the Indian population in KwaZulu-Natal. We randomly selected 250 apparently healthy Indians, aged 35-55 years, living in KwaDukuza to participate in this study. Clinical and anthropometric measurements were taken under prescribed clinical conditions using Asian cut-off points. Pearson correlations was used to detect associations between anthropometric and clinical risk markers. A large percentage of participants' systolic blood pressure fell within the normal range. Diastolic blood pressure was >85 mmHg for 61 % of the participants and triglyceride levels were >1.69 mmol/L for 89 % of the participants'; 94 % of the women and 87 % of the men were classified as centrally obese. Raised fasting blood glucose was seen in 39 % of participants'. Waist circumference and body mass index showed statistically significant associations with all clinical risk markers except for diastolic blood pressure. Our findings suggest that the use of ethno specific strategies in the management of the disease profile of South African Indians, will enable the South African health system to respond more positively towards the current trend of increased metabolic and physiological risk factors in this community. Moreover, key modifiable behaviours such as increased physical activity and weight reduction may improve most of these metabolic abnormalities.

Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial.

BACKGROUND: Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. METHODS: Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. RESULTS: No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. CONCLUSIONS: The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

[Prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China].

Objective: The purpose of this study was to investigate the prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China. Methods: A total of 20 194 participants aged ≥18 years were selected randomly by cluster sampling from two townships(towns)in Henan Province from July to August 2007 and July to August 2008. Investigations included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination at baseline. A total of 16 155 participants were followed up from July to August 2013 and July to October 2014. Overall, 13 869 participants were included in the study, after excluding 2 286 participants with incomplete dyslipidemia follow-up data. Distributions of the characteristics of dyslipidemia were determined, and prevalence was standardized by age according to data of the 2010 Sixth National Population Census. Risk factors for dyslipidemia were analyzed using a logistic regression model after adjusting for sex, age, education level, marital status, and income status. Results: The prevalence of dyslipidemia was 53.72%(7 450/13 869)for residents aged ≥22 years living in rural areas of Henan Province(59.32%(3 069/5 174)for men and 50.39%(4 381/8 695)for women). The adjusted prevalence of dyslipidemia was 50.50%(59.27% for men and 45.53% for women). The prevalence of hypercholesterolemia, hypertriglyceridemia, low HDL-C, and high LDL-C was 4.34%(602/13 868), 20.42%(2 826/13 837), 42.75%(5 927/13 865), and 3.14%(420/13 375), respectively, and the adjusted prevalence was 2.44%, 18.84%, 41.42%, and 1.86%, respectively. Logistic regression analyses showed that alcohol consumption(OR=1.27, 95% CI: 1.05-1.53), family history of hyperlipidemia(OR=1.29, 95% CI: 1.17-1.43), overweight(OR=1.40, 95% CI: 1.22-1.61), obesity(OR= 1.65, 95% CI: 1.39- 1.96), abnormal waist circumference(OR=1.22, 95% CI: 1.04- 1.43), and abnormal waist-height ratio(OR=1.21, 95% CI: 1.01-1.45)were significant independent risk factors, and high levels of physical activity(OR=0.85, 95% CI: 0.77- 0.95)and underweight(OR=0.52, 95% CI: 0.36- 0.75)were protective factors for dyslipidemia after adjusting for sex, age, education level, marital status, and income status. Conclusion: The prevalence of dyslipidemia was very high for this rural population. Alcohol consumption, family history of hyperlipidemia, overweight, obesity, abnormal waist circumference, and abnormal waist-height ratio were significant independent risk factors for dyslipidemia.

[Epidemiological characteristics of dyslipidemia in remote rural areas of Xinjiang, 2009-2010].

Objective: This study aimed to estimate the prevalence of dyslipidemia, hypertriglyceridemia, hypercholesterolemia, high blood low density lipoprotein cholesterol (LDL-C), and low blood high density lipoprotein cholesterol (HDL-C) in remote rural areas of Xinjiang and analyze these indicators' epidemiological characteristics. Methods: A survey of 13 000 individuals (aged ≥18 years) was conducted using a four-stage cluster random sampling method in Jiashi, Xinyuan, Aheqi, and Shawan Counties, Xinjiang, in 2009-2010. After nonpermanent residents were excluded, 12 154 individuals were included in this study. Questionnaire and physical examinations were conducted, including collection of fasting blood to detect TG, TC, LDL-C, and HDL-C. The results were calculated after complex weighting and compared according to the prevalence of different gender and age groups. Results: The overall levels of TG, TC, LDL-C, and HDL-C were 1.34±1.09, 4.45±1.16, 2.36±0.86, and 1.37±0.58 mmol/L, respectively. After complex weighting, the overall prevalence of dyslipidemia was 35.4%; that among men (42.9%) was greater than that among women (29.5%; χ2=234.19, P<0.001), and the prevalence was 35.9%, 34.5%, and 35.1% (χ2=1.52, P=0.467) in participants aged 18-44, 45-59, and ≥60 years, respectively. The overall prevalence of hypertriglyceridemia was 11.4%; that among men (13.5%) was greater than that among women (9.8%; χ2= 40.72, P<0.001), and the prevalence was 9.6%, 13.0%, and 13.2% (χ2=38.71, P<0.001) in participants aged 18-44, 45-59, and ≥60 years, respectively. The prevalence of hypercholesterolemia was 5.7%; that among men(5.0%) was greater than that among women (6.2%; χ2=6.95, P=0.008), and the prevalence was 3.5%, 7.4%, and 8.4% (χ2=105.24, P<0.001) in participants aged 18-4, 45-59, and ≥60 years, respectively. The prevalence of high blood LDL-C was 2.8%, and there was no significant difference between men (3.0%) and women (2.4%; χ2=1.43, P=0.231); the prevalence was 3.5%, 7.4%, and 8.4% (χ2=42.81, P<0.001) in participants aged 18-44, 45-59, and ≥60 years, respectively. The prevalence of low blood HDL-C was 24.0%; that among men (31.6%) was greater than that among women (18.0%; χ2=304.02, P<0.001), and the prevalence was 27.8%, 20.6% and 19.5% (χ2=96.61, P<0.001) in participants aged 18-44, 45-59, and ≥ 60 years, respectively. Conclusions: Low blood HDL-C was the main type of dyslipidemia among the population in remote rural areas of Xinjiang. The prevalence of dyslipidemia among men was greater than that among women, and there was a trend of younger men than women showing dyslipidemia.

The hypertriglyceridemic-waist phenotype is associated with the Framingham risk score and subclinical atherosclerosis in Canadian Cree.

BACKGROUND AND AIMS: For primary prevention of cardiovascular disease (CVD), Canadian guidelines recommend that asymptomatic Canadians with abdominal obesity undergo Framingham risk score (FRS) assessment, and that in Indigenous Peoples, indicators of metabolic syndrome also be used to identify at-risk individuals. The hypertriglyceridemic-waist phenotype (HTGW) has been proposed to be a surrogate marker of visceral obesity and a simple proxy measure for metabolic syndrome. The primary aim of this study was to evaluate whether the HTGW and the FRS associated with sub-clinical atherosclerosis. METHODS AND RESULTS: Asymptomatic Cree participants in a cross-sectional study conducted 2005-2009 (n = 446, 18-81 y) were assessed for the HTGW using NCEP-ATP-III gender-specific-cutoffs (waist circumference: for men, ≥102 cm; for women ≥88 cm) and fasting triglycerides ≥1.7 mmol/L. Sub-clinical atherosclerosis was defined by the presence of a high sex-specific common-carotid-intimal-medial-wall-thickness (≥75th percentile). HTGW was present in 26.7% and a 10-y FRS greater than 10% was present in 18.8% of participants. The multivariate adjusted OR (95% CI) for sub-clinical atherosclerosis associated with an FRS greater than 10% was 4.10 (2.20-7.50) while that associated with the HTGW phenotype was 1.74 (95% CI 1.61-1.88) from a model including age, body mass index, alcohol consumption, FRS and the HTGW. CONCLUSIONS: The HTGW phenotype is prevalent in the Cree. Our findings support further study on the utility of combining the HTGW with the FRS in the prediction of cardiovascular disease outcomes and in health screening and intervention programs among indigenous peoples.

Polygenic risk for hypertriglyceridemia is attenuated in Japanese men with high fitness levels.

High cardiorespiratory fitness (CRF) is associated with a reduced risk for dyslipidemia; however, blood lipid levels are also affected by individual genetic variations. We performed a cross-sectional study to determine whether CRF modifies polygenic risk for dyslipidemia. Serum levels of triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) were measured in 170 Japanese men (age 20-79 yr). CRF was assessed by measuring maximal oxygen uptake (Vo2max), and subjects were divided into low-fitness and high-fitness groups according to the reference Vo2max value for health promotion in Japan. We analyzed 19 single nucleotide polymorphisms (SNPs) associated with TG, LDL-C, or HDL-C levels. Based on these SNPs, we calculated three genetic risk scores (GRSs: TG-GRS, LDL-GRS, and HDL-GRS), and subjects were divided into low, middle, and high groups according to the tertile for each GRS. Serum TG levels of low-fitness individuals were higher in the high and middle TG-GRS groups than in the low TG-GRS group (P < 0.01 and P < 0.05, respectively), whereas no differences were detected in the TG levels of high-fitness individuals among the TG-GRS groups. In contrast, the high LDL-GRS group had higher LDL-C levels than did the low LDL-GRS group, and HDL-C levels were lower in the high HDL-GRS group than in the low HDL-GRS group regardless of the fitness level (P < 0.05). These results suggest that high CRF attenuates polygenic risk for hypertriglyceridemia; however, high CRF may not modify the polygenic risk associated with high LDL-C and low HDL-C levels in Japanese men.

Optimal cutoff of the waist-to-hip ratio for detecting cardiovascular risk factors among Han adults in Xinjiang.

BACKGROUND: The optimal cutoff of the waist-to-hip ratio (WHR) among Han adults in Xinjiang, which is located in the center of Asia, is unknown. We aimed to examine the relationship between different WHRs and cardiovascular risk factors among Han adults in Xinjiang, and determine the optimal cutoff of the WHR. METHODS: The Cardiovascular Risk Survey was conducted from October 2007 to March 2010. A total of 14618 representative participants were selected using a four-stage stratified sampling method. A total of 5757 Han participants were included in the study. The present statistical analysis was restricted to the 5595 Han subjects who had complete anthropometric data. The sensitivity, specificity, and distance on the receiver operating characteristic (ROC) curve in each WHR level were calculated. The shortest distance in the ROC curves was used to determine the optimal cutoff of the WHR for detecting cardiovascular risk factors. RESULTS: In women, the WHR was positively associated with systolic blood pressure, diastolic blood pressure, and serum concentrations of serum total cholesterol. The prevalence of hypertension and hypertriglyceridemia increased as the WHR increased. The same results were not observed among men. The optimal WHR cutoffs for predicting hypertension, diabetes, dyslipidemia and ≥ two of these risk factors for Han adults in Xinjiang were 0.92, 0.92, 0.91, 0.92 in men and 0.88, 0.89, 0.88, 0.89 in women, respectively. CONCLUSIONS: Higher cutoffs for the WHR are required in the identification of Han adults aged ≥ 35 years with a high risk of cardiovascular diseases in Xinjiang.

Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.

BACKGROUND: The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. METHODS AND FINDINGS: We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein gene (p=2.43×10(-08)). Furthermore, three European loci for TGs (APOA5, GCKR and LPL), and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We used cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalised to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. CONCLUSIONS: This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; used the interpopulation heterogeneity to significantly restrict three previously known European GWA signals, and surveyed whether the European lipid GWA SNPs extend to the Mexican population.

Anthropometry for predicting cardiometabolic disease risk factors in adolescents.

OBJECTIVE: Early screening prevents chronic diseases by identifying at-risk adolescents through anthropometric measurements, but predictive value in diverse groups is uncertain. METHODS: A cross-sectional analysis of 12- to 19-year-old individuals from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) assessed the predictive ability of BMI percentile, total body fat percentage, waist circumference (WC), and waist-hip ratio (WHR) for four cardiometabolic risk factors across race and ethnicity groups using receiver operating characteristic curves. RESULTS: The unweighted sample (N = 1194; 51.2% male individuals; 23.7% Hispanic, 13.2% non-Hispanic Black [NHB], 51.1% non-Hispanic White [NHW], 12.0% other/multirace) had a weighted prevalence of elevated blood pressure of 2.7%, hyperglycemia of 36.8%, hypertriglyceridemia of 4.8%, and low high-density lipoprotein (HDL) cholesterol of 15%. WHR (area under the curve [AUC] = 0.77), WC (AUC = 0.77), and BMI percentile (AUC = 0.73) outperformed total body fat percentage (AUC = 0.56) in predicting elevated blood pressure (p < 0.001 for all). BMI percentile was more accurate than total body fat percentage in predicting hypertriglyceridemia (AUC = 0.70 vs. 0.59; p = 0.02) and low HDL cholesterol (AUC = 0.69 vs. 0.59; p < 0.001). Race and ethnicity-based predictions varied: NHW adolescents had the highest AUC (0.89; p < 0.01) for elevated blood pressure prediction compared with Hispanic and NHB adolescents (AUC = 0.77 for both). Total body fat percentage was more accurate in predicting low HDL cholesterol among Hispanic versus NHW adolescents (AUC = 0.73 vs. 0.58; p = 0.04). CONCLUSIONS: WHR, WC, and BMI percentile are better predictors of cardiometabolic risk factors in adolescents than total body fat percentage. Predictive abilities differed by race and ethnicity, highlighting the importance of tailored risk assessment strategies.

The g.-469G>A polymorphism in the GPIHBP1 gene promoter is associated with hypertriglyceridemia and has an additive effect on the risk conferred by LPL defective alleles.

BACKGROUND AND AIMS: Hypertriglyceridemia (hyperTG) is a component of the metabolic syndrome and a cardiovascular or pancreatitis risk factor. Although both genetic and environmental factors influence its expression, the biological component of hyperTG is still underestimated and has been reported in 10-20% of cases only. Given its key role in the lipolysis of TG-rich lipoproteins, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) is a biological candidate for hyperTG. The aim of this study was to assess the association of new GPIHBP1 gene variants with hyperTG (fasting plasma TG values ≥ 2.0 mmol/L). METHODS AND RESULTS: Sequencing the GPIHBP1 gene identified a g.-469G > A (rs72691625) polymorphism in the promoter. A sample of 541 Caucasians (263 normoTG and 278 hyperTG) was then screened for this polymorphism using a 5'nuclease TaqMan. In multivariate analyses, GPIHBP1 g.-469G > A polymorphism carriers were at significantly higher risk of hyperTG (≥ 2.0 mmol/L) than non-carriers, the odds ratio (OR) being 1.67 (p = 0.025) among heterozygotes and 5.70 (p = 0.004) in homozygotes. The simultaneous presence of loss-of-function LPL polymorphisms had an incremental additive effect on the risk of hyperTG (OR: 7.30; p < 0.001), highlighting the importance of gene-gene interactions in the expression of hyperTG. CONCLUSIONS: In this study, the g.-469G >A polymorphism in the GPIHBP1 gene promoter was associated with an increased risk of hyperTG and had an additive effect on the risk conferred by LPL defective alleles.

Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of therapy in most strategies of dyslipidaemia management focused on cardiovascular disease prevention. Different guidelines have identified specific LDL-C cut-off points as targets for therapeutic intervention. Many clinical situations characterised by dyslipidaemia and elevated triglycerides are common in our environment and in overall industrialised countries. Thus, lipid goals based only on LDL-C could misclassify an important percentage of subjects. The objective of the present study was to establish cut-off point values for apoB and non-HDL-C in relation to the identified LDL-C cut-off points for cardiovascular risk in a South European population. METHODS: We performed a cross-sectional study including 1501 subjects (770 women and 731 men) between 18 and 80 years of age. Samples were collected after 12-14 h of fasting. Cholesterol, HDL-C, triglycerides and apoB levels were measured using direct methods. LDL-C was calculated by the Friedewald formula. Non-HDL-C was calculated as total cholesterol minus HDL-C. RESULTS: The Spearman's rank correlations between apoB and LDL-C (r 0.86, p < 0.0001), and between apoB and non-HDL-C (r 0.91, p < 0.0001) were both significant. The proposed cut-off points for apoB, according to LDL-C goals (70, 100, 130 and 160 mg/dl) in our population are 70, 80, 100 and 115 mg/dl respectively. The proposed cut-off values for non-HDL-C are 100, 120, 150 and 190 mg/dl respectively. CONCLUSION: The established LDL-C cut-off values could not be accurate to estimate cardiovascular risk in subjects with mild hypertriglyceridaemia, as frequently occurs in our Mediterranean population. To take into consideration the burden of atherogenic particles and better classify patients at risk we propose cut-off values for apoB or the equivalent for non-HDL-C. Prospective trials including cardiovascular variables are needed to validate our assumption.

Depression, cardiometabolic function and left ventricular hypertrophy in African men and women: the SABPA study.

Depressive symptoms are associated with an increased risk for developing cardiovascular diseases, driven by its link to the metabolic syndrome (MetS). This phenomenon, however, still needs to be investigated in the African population. The aim of this study is to investigate the association between left ventricular hypertrophy (LVH) and MetS risk markers in a determined sample. The researchers stratified Black African men and women into with depressive symptoms (D) or without depressive symptoms (ND) group, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria score. Fasting MetS, chronic hyperglycemia (HbA1c), ambulatory blood pressure (BP) and Cornell product-LVH (CP-LVH) in ECG measures were obtained. Depressive symptoms were reported in 45.3% of the sample. Independent of depression status, African men and women revealed a pre-diabetic state (glycated hemoglobin >5.7%). CP-LVH was associated with decreased low high-density lipoprotein cholesterol in D African women. In D African men, systolic BP (P = .001) and HbA1c (P = .08) explained 64% and 31% of the variation in LVH, respectively. In conclusion, depressive symptoms in Black African women were associated with a measure of target end organ damage, CP-LVH, and this association was driven by a metabolic factor. In Black African men, independent of depressive symptoms, LVH, was driven by cardiometabolic factors, namely SBP and HbA1c.

Hypertriglyceridemic waist, cytokines and hyperglycaemia in Chinese.

BACKGROUND: Abdominal obesity and hypertriglyceridemia confer high risk for cardiometabolic disease. Few studies have investigated the associations of hypertriglyceridemic waist with cytokines and hyperglycaemia in Chinese. METHODS: Anthropometric indexes, fasting plasma concentrations of glucose, glycohemoglobin, insulin, lipid profile, inflammatory factors and adipokines were measured among 3289 Chinese men and women 50-70 years of age. RESULTS: An increment of every 2 cm of waist circumference was associated with increased levels of high-sensitive C-reactive protein (hsCRP), interleukin 6 and RBP 4 by 0·033 mg/L, 0·018 ng/L and 0·556 mg/L and reduced levels of adiponectin by 0·269 mg/L (all P<0·05), respectively, with controlling for potential confounders. For triglycerides, each an increment of 20 mg/dL was associated with increased levels of hsCRP, RBP4, and decreased levels of adiponectin by 0·021 mg/L, 0·655 mg/L, and 0·371 mg/L (all P<0·05), respectively. Individuals with hypertriglyceridemic waist had increased risks of having hyperglycaemia (OR: 1·48; 95% CI: 1·09, 2·00) and diabetes mellitus (OR: 2·12; 95% CI: 1·47, 3·04) compared with those with neither of the phenotypes. CONCLUSIONS: Hypertriglyceridemic waist is associated with a worse profile of inflammatory factors and adipokines as well as with an increased risk of having hyperglycaemia among Chinese.