Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease.

MicroRNAs (miRs) regulate gene expression at the post-transcriptional level and are found to be present in monocytes. This study aimed to investigate miR-221-5p, miR-21-5p, and miR-155-5p, their expression in monocytes, and their role in coronary arterial disease (CAD). The study population comprised 110 subjects, and RT-qPCR was used to examine the miR-221-5p, miR-21-5p, and miR-155-5p expressions in monocytes. Results: the miR-21-5p (p = 0.001) and miR-221-5p (p < 0.001) expression levels were significantly higher in the CAD group, and the miR-155-5p (p = 0.021) expression levels were significantly lower in the CAD group; only miR-21-5p and miR-221-5p upregulation was found to be associated with an increased CAD risk. The results show significant increases in miR-21-5p in the unmedicated CAD group with the metformin patients vs. the healthy control group (p = 0.001) and vs. the medicated CAD group with metformin (p = 0.022). The same was true for miR-221-5p in the CAD patients unmedicated with metformin vs. the healthy control group (p < 0.001). Our results from Mexican CAD patients show that the overexpression in monocytes of miR-21-5p and miR-221-5p increases the risk of the development of CAD. In addition, in the CAD group, the metformin downregulated the expression of miR-21-5p and miR-221-5p. Also, the expression of endothelial nitric oxide synthase (NOS3) decreased significantly in our patients with CAD, regardless of whether they were medicated. Therefore, our findings allow for the proposal of new therapeutic strategies for the diagnosis and prognosis of CAD and the evaluation of treatment efficacy.

Challenges around Child-Feeding Practices with 'Comida Chatarra': A Qualitative Study to Understand the Role of Sociocultural Factors in Caregiver Feeding Decisions.

A massive incorporation of ultra-processed products into young children's diets worldwide and in Mexico has been documented. The aim of this study is to understand the role of sociocultural factors in principal caregivers' decisions to give a type of ultra-processed food to children under age five, called 'comida chatarra' ('junk food' in English), usually includes sugar-sweetened beverages, sweet and salty snacks, and sweet breakfast cereals. We conducted a descriptive, observational qualitative study. The research was conducted in urban and rural communities in two Mexican states. Twenty-four principal caregivers were equally distributed between the two states and types of communities. They were interviewed in person. Phenomenology underpinned this study. Results highlight the preponderant role of culture in food choices and feeding practices with junk food. Local culture influences child-feeding with ultra-processed products through social norms, knowledge, or socially constructed attitudes. These social norms, built in the context of abundant ultra-processed products and omnipresent marketing, 'justify' children's consumption of junk food. They acquire these products from the principal caregivers, family members, and neighbors, among others, who reward and pamper them. These actors also define what amount (small amounts) and when (after meals as snacks) children are given these products. Cultural factors must be considered in the development of effective public policies and programs that aim to change the culture around ultra-processed products among children and avoid their consumption.

Spatial and seasonal dynamics of the methane cycle in a tropical coastal lagoon and its tributary river.

Coastal aquatic ecosystems such as estuaries and coastal lagoons are important atmospheric methane sources that must be better constrained. This work presents a detailed characterization of the methane cycle in a tropical coastal lagoon (La Mancha, Veracruz, Mexico) and its tributary river over three distinct seasons, along a transect from the river to the sea connection. In addition to several physicochemical parameters, the dissolved methane, carbon dioxide, and oxygen concentrations were measured with high resolution in the sediments and the water column, combined with production/uptake rates. Methane and carbon dioxide cycles were further constrained by determining atmospheric flux over the entire river and lagoon sections. The results indicate that La Mancha is a highly contrasted ecosystem. The river section is characterized by a strong pycnocline, relatively high methane concentration, and active methanogenesis and methanotrophy, discharging into a relatively homogeneous lagoon section where the methane and carbon cycles are less active. Overall, both the river and the lagoon were a net source of methane and carbon dioxide, with an annual emission of 2.9 metric tons of methane and 2757 metric tons of carbon dioxide. The spatial structure of the main components of the methane, carbon dioxide, and oxygen cycles was established, and it was observed that depthwise heterogeneities predominated in the river section. In contrast, lengthwise heterogeneities dominated in the lagoon section.

Familial hypercholesterolemia in Mexico: Initial insights from the national registry.

BACKGROUND: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. OBJECTIVE: Report the results of the first years (2017-2019) of the Mexican FH registry. METHODS: There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations. RESULTS: To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C <100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033). CONCLUSION: The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.

Association between the transporters ABCA1/G1 and the expression of miR-33a/144 and the carotid intima media thickness in patients with arterial hypertension.

ATP-binding cassette membrane transporters (ABC), functions as an outflow facilitator of phospholipids and cellular cholesterol, playing an important role in the development of atherosclerosis and arterial hypertension. ABC's transporters could post-transcriptionally regulated by miRs. Evaluate the association in the transporters ABCA1 and ABCG1 with the expression of miR-33a and miR-144 and the carotid intima media thickness (cIMT) in patients with essential arterial hypertension. The miR-33a-5p, miR-144-3p and mRNA ABCA1 and ABCG1 expression in monocytes from Mexican hypertensive patients were examined by RT-PCR. The miR-33a and miR-144 expression in monocytes and mRNA ABCA1 and ABCG1 from Mexican hypertensive patients were examined by RT-PCR. This study involved 84 subjects (42 normotensive subjects and 42 patients with essential hypertension). Our study revealed that miR-33a expression (p = 0.001) and miR-144 (p = 0.985) were up-regulated, meanwhile, ABCA1 and ABCG1 transporters were down-regulated (p = 0.007 and p = 0.550 respectively) in hypertensive patients compared with the control group. The trend remains for miR33a/ABCA1 in presence of cIMT. Moreover, an inverse correlation was found with the expression levels of ABCA1 and ABCG1 as well as in HDL-C with miR-33a and miR-144. Our results showed an increase in the expression of miR-33a and miR-144 and an inverse correlation in their target ABCA1 and ABCG1; it may be associated with essential arterial hypertension in patients with cIMT and as consequence for atheromatous plaque.

Sociocultural Influences on Poor Nutrition and Program Utilization of Mexico's Conditional Cash Transfer Program.

BACKGROUND: The impact of the Conditional Cash Transfer Program in Mexico was significant but smaller than expected. Several bottlenecks related to program design and implementation have been identified that may have limited its impact; population and other contextual factors may be equally important to analyze. OBJECTIVES: We aimed to explore how sociocultural context contributes to poor nutrition in Mexico and how it shaped the acceptability, fidelity, and penetration of the fortified food and of education sessions provided by the program. METHODS: We carried out qualitative research studies in the central and southern states in urban, rural, and indigenous settings between 2001 and 2014 with different informants and by using interviews, focus group discussions, and nonparticipatory observation. We explored 4 dimensions of the sociocultural context: objective dimension (e.g., food availability and family organization), social norms and symbolic meaning related to child feeding, literacy and communication with the biomedical culture, and knowledge related to child care generally and child feeding. We generated information about the experience of the beneficiaries with fortified food and education sessions. RESULTS: Several sociocultural factors, including patriarchal family organization, high availability of nonnutritious food, social norms promoting the consumption of food in liquid form for young children, sharing of food among family members, traditional knowledge, and communication barriers with the biomedical culture, participated in shaping the poor nutrition situation, the inadequate utilization of fortified foods, and the inappropriateness of the education sessions. CONCLUSIONS: Our studies revealed the importance of local context and culture to understand the acceptance, utilization, and impact of a nutrition program and shed light on infant and child feeding practices. This knowledge is critical to strengthen program designs and ensure adequacy with the diversity of cultural and social contexts in which programs are implemented.

Translating Evidence-Based Program Recommendations into Action: The Design, Testing, and Scaling Up of the Behavior Change Strategy EsIAN in Mexico.

BACKGROUND: The Integrated Strategy for Attention to Nutrition (EsIAN in Spanish) is a national strategy within Mexico's conditional cash transfer program (initially Progresa, then Oportunidades, then Prospera, CCT-POP) designed to strengthen the health and nutrition component, address the nutrition transition, and improve the health and nutritional status of its beneficiaries, through 3 main components: 1) procurement of functioning equipment to primary health care (PHC) units; 2) providing free micronutrient supplements to beneficiary women and children; 3) implementing a behavior change communication (BCC) strategy and a training system for PHC providers (PHCPs). OBJECTIVE: We aim to describe the iterative process and evidence-based approach used to design and roll-out the EsIAN at scale, by focusing on the BCC component. METHODS: The BCC strategy was developed by following an iterative process through the following phases: situational analysis, formative research and design of the BCC strategy (using the socioecological framework and the social marketing approach), large-scale feasibility study, redesign, and national scale-up. RESULTS: The review and formative research revealed several barriers and issues that limited program coverage, utilization, and acceptance. These included misconceptions about pregnancy and infant feeding, nonalignment of practices with international recommendations, and lack of knowledge on nutrition and related topics, among others. These results were used to identify priority behaviors and elaborate key messages for mothers/caregivers and providers to develop the BCC strategy. The feasibility study resulted in significant improvements in PHCPs' knowledge, counseling (breastfeeding, and supplement use and consumption), and caregivers' complementary feeding behaviors, and highlighted several design and delivery aspects that needed strengthening. Based on these findings, the BCC strategy was adapted prior to a national scale-up. CONCLUSIONS: The theory-based iterative approach resulted in the identification of specific actions to target, and approaches to do so, as part of the design and roll-out of the BCC strategy at scale.

Type 2 Diabetes Mellitus is Associated with Carotid Artery Plaques in Patients with Premature Coronary Heart Disease.

BACKGROUND: In subjects without a history of coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) is associated with carotid artery plaques (CAP), which is a better marker than high carotid intima-media thickness (hCIMT) for predicting first or recurrent cardiovascular events. OBJECTIVE: The objective of this study is to analyze the association of T2DM with CAP and hCIMT in premature CHD patients. METHODS: Premature CHD was considered before the age of 55 years in men and before 65 in women. T2DM was defined according to the American Diabetes Association criteria. CAP was defined as a focal structure encroaching the arterial lumen by at least 50% of the surrounding IMT value or with a thickness > 1.5 mm. RESULTS: Among 1196 patients (CHD duration 1.5 years [interquartile range: 0.4-5.6]), 37.2% had T2DM, and 97.8% were on antihypertensive, 94.4% on lipid-lowering, and 97.3% on anti-aggregate treatment. hCIMT prevalence was similar in patients with or without T2DM, whereas CAP prevalence was higher among T2DM patients (17.7% vs. 30.9%; p < 0.001). T2DM showed association with CAP, independently of CHD evolution and glycemic control (odds ratio: 1.57; 95% confidence interval: 1.09-2.26). CONCLUSIONS: T2DM has an independent association with CAP. Early detection of recurrent cardiovascular events, with CAP identification, could be useful to prevent complications in patients with CHD.

Increased expression of miR-33a in monocytes from Mexican hypertensive patients in elevated carotid intima-media thickness.

miR-33a has been described as a key regulator in the initiation and progression of atherosclerosis. However, its role in arterial hypertension (HTA) has not been elucidated. Therefore, the aim of this study was to determine the association between the expression of miR-33a (5p and 3p) and the carotid intima-media thickness (cIMT) in samples of monocytes and serum from hypertensive patients. The miR-33a-5p and miR-33a-3p expression in monocytes and serum from Mexican hypertensive patients were examined by RT-PCR. This study involved 84 subjects (42 normotensive subjects and 42 patients with essential hypertension). Our study revealed that miR-33a-5p expression was significantly upregulated in the monocytes of hypertensive patients compared with the control group (p = 0.001), while miR-33a-3p was significantly downregulated (p = 0.013). miR-33a-5p upregulation [OR: 5.53, 95% CI: 2.01-15.20; p = 0.001], as well as miR-33a-3p downregulation [OR: 3.32, 95% CI: 1.45-7.60; p = 0.004] in monocytes, was associated with an increased risk of developing hypertension. In addition, miR-33a-5p upregulation in hypertensive patients was associated with an increased risk of presenting cIMT [OR: 5.99, 95% CI: 1.10-32.85; p = 0.039]. Moreover, we found no significant differences in the expression of both strands of miR-33a in serum of our patients. Our results showed an upregulation of miR-33a-5p and downregulation of miR-33a-3p in monocytes, these data are associated with cIMT, which could be a risk factor for the development of hypertension. In addition, upregulation of miR-33a-5p in monocytes from Mexican hypertensive patients could be involved in the development of atherosclerosis.

Microalbuminuria and its Association with Subclinical Atherosclerosis in the Mexican Mestizo population: the GEA study.

BACKGROUND: Microalbuminuria is an early marker of atherosclerosis. Ethnic differences for both conditions have been reported. We studied microalbuminuria prevalence and its association with coronary artery calcification as an early atherosclerosis marker in a Mexican-Mestizo population free of diabetes and hypertension (healthy), as well as in hypertensive and diabetic subjects. METHODS: In 1,472 adults (53.3 ± 9.4 years old, 50.3% women), anthropometric measurements, fasting blood glucose, and lipid profile were determined. A spot urine sample was used to quantify the albumin-to-creatinine ratio and to define microalbuminuria (20-200 mg/g in men, and 30-300 mg/g in women). A coronary artery calcification score was obtained by electron-beam computed tomography and subclinical atherosclerosis was defined as a score > 0. RESULTS: Overall microalbuminuria prevalence was 9.3% (5.4% in healthy, 11.6% in obese, 12% in hypertensive, and 25% in diabetic subjects). Compared to "healthy" subjects without microalbuminuria, those with microalbuminuria had a ∼3-fold higher prevalence of coronary artery calcification > 0, while normal-high albumin-to-creatinine ratio (OR: 1.8; p < 0.05) and microalbuminuria (OR: 2.6; p < 0.001) was independently associated with coronary artery calcification > 0 only among diabetic subjects. CONCLUSIONS: Microalbuminuria and high-normal albumin-to-creatinine ratio were independently associated with subclinical atherosclerosis, suggesting that they may confer a higher risk of future cardiovascular events.

The variant rs8048002 T>C in intron 3 of the MHC2TA gene is associated with risk of developing acute coronary syndrome.

Recently, an intronic single nucleotide polymorphism (rs8048002) in the MHC class II transactivator gene (MHC2TA) was shown to be associated with increased susceptibility to several inflammatory diseases. The aim of the present study was to test for an association between this MHC2TA gene polymorphism and susceptibility to the risk of developing acute coronary syndromes (ACS) in a group of Mexicans patients. The single nucleotide polymorphism (rs8048002) of the MHC2TA gene was analyzed by 5' exonuclease TaqMan genotyping assays in a group of 452 patients with ACS and 456 healthy controls. The C allele and TC genotype were associated with risk of developing ACS (OR=4.55, pC=6×10(-4) and OR=4.41, pC=1.5×10(-3), respectively). Multiple logistic analysis was used for estimate risk between ACS patients and controls adjusted by cardiovascular risk factors (gender, age, hypertension, dyslipidemia, smoking, diabetes, body mass index and alcohol consumption). In this analysis, the TC+CC genotypes were significantly associated with increased risk of ACS as compared to TT genotype (OR=4.56, pC=0.004). In summary, our data suggest that the MHC2TA rs8048002 C>T gene polymorphism plays an important role in the risk of developing ACS.

Premature and severe cardiovascular disease in a Mexican male with markedly low high-density-lipoprotein-cholesterol levels and a mutation in the lecithin:cholesterol acyltransferase gene: a family study.

Epidemiological and clinical studies have shown that a low plasma high­density lipoprotein cholesterol (HDL-C) level is a strong predictor of cardiovascular disease (CVD). Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the formation, maturation and function of HDL. Therefore impaired LCAT function may enhance atherosclerosis because of defective cholesterol transport. In this study, we examined a 34-year old LCAT­deficient patient and eight first-degree family members. There was a strong family history for CVD and type 2 diabetes mellitus (DM2). The proband was found homozygous for a previously reported LCAT gene mutation (Thr37Met). A sister and two sons of the proband were heterozygous for the same mutation. The proband had DM2 and showed severe multivessel coronary artery disease, corneal opacification and extremely low HDL-C levels. Large HDL particles were absent while small HDL particles were increased. The HDL of the patient had a reduced ability to promote cell cholesterol efflux, and the low­density lipoproteins (LDL) were more susceptible to oxidation. Among his family members, two heterozygotes and one non-carrier had early carotid or coronary atherosclerosis. In conclusion, as the increased LDL oxidability and structural and functional abnormalities of HDL particles have been reported in patients with obesity and diabetes, the results suggested that the adverse coronary risk profile, and not being LCAT deficient, may be responsible for the CVD found in our proband, and for the early atherosclerosis observed in the two heterozygotes and in the wild­type family members.

[Dietary patterns and physical activity in the mexican population: association with fatty liver]. / Patrones dietarios y de actividad física en población mexicana: asociación con hígado graso.

INTRODUCTION: Non-alcoholic fatty liver (FL) has a high prevalence and is associated with clinical conditions such as dyslipidemia, arterial hypertension, diabetes, and coronary artery disease. OBJECTIVE: To investigate the association of physical activity (PA) and nutritional factors on the presence of FL, and to analyze the association of the energy intake/energy expenditure (EI/EE) index with FL. METHODS: We studied 786 nondiabetic subjects without a history of hepatic or cardiovascular disease, and alcohol consumption < 20 g/d. Diet and PA were assessed using standardized questionnaires, and visceral abdominal fat (VAF) and liver fat by tomography. The energy intake/energy expenditure (EI/EE) index effect on the presence on FL was analyzed. RESULTS: No macronutrient was associated with FL. After adjusting for age, gender, VAF, and total kilocalories, PA significantly reduced the risk of FL (OR: 0.86; 95% CI: 0.74-0.99; p = 0.03). In logistic regression analysis adjusted for confounding factors, the EI/EE index was associated with the presence of FL (OR: 1.69; 95% CI: 1.02-2.82; p = 0.04). CONCLUSION: These results suggest that independent of macronutrient composition, a high hypercaloric diet with physical inactivity favours the development of fatty liver.

Fatty liver increases the association of metabolic syndrome with diabetes and atherosclerosis.

OBJECTIVE: To analyze the participation of fatty liver (FL) in the association of metabolic syndrome (MS) with type 2 diabetes and coronary artery calcification (CAC). RESEARCH DESIGN AND METHODS: A total of 765 subjects (52% women) aged 30 to 75 years without clinical atherosclerosis were included in this study. MS was defined in accordance with the Adult Treatment Panel III (ATPIII) guidelines, while FL and CAC were identified by computed tomography. RESULTS: There were increasing frequencies of type 2 diabetes and CAC in all three groups: control, MS without FL, and MS plus FL. Multivariable-adjusted logistic regression analyses showed that FL increased the association of MS with type 2 diabetes in both women [odds ratio 10.6 (95% CI 3.4-33.7)] and men [12.1 (4.1-36.1)]. In women, FL also increased the association of MS with CAC [2.34 (1.07-5.12)]. CONCLUSIONS: FL increases the association of MS with type 2 diabetes and subclinical atherosclerosis.

The ABCA1 gene R230C variant is associated with decreased risk of premature coronary artery disease: the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: ABCA1 genetic variation is known to play a role in HDL-C levels and various studies have also implicated ABCA1 variation in cardiovascular risk. The functional ABCA1/R230C variant is frequent in the Mexican population and has been consistently associated with low HDL-C concentrations. Although it has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD). AIM: The purpose of the study was to analyze whether the ABCA1/R230C variant is associated with premature CAD in a case-control association study (GEA or Genetics of Atherosclerotic Disease), and to explore whether BMI modulates the effect of the C230 allele on other metabolic traits using a population-based design. RESULTS: The C230 allele was significantly associated with both lower HDL-C levels and a lower risk of premature CAD as compared to controls (OR = 0.566; P(add) = 1.499×10(-5)). In addition, BMI modulated the effect of R230C on body fat distribution, as the correlation between BMI and visceral to subcutaneous adipose tissue (a metric of the propensity to store fat viscerally as compared to subcutaneously) was negative in RR homozygous individuals, but positive in premenopausal women bearing the C230 allele, with a statistically significant interaction (P = 0.005). BMI-R230C interaction was also significant for triglyceride levels in women regardless of their menopausal status (P = 0.036). CONCLUSION: This is the first study assessing the effect of the R230C/ABCA1 variant in remature CAD. C230 was associated with both decreased HDL-C levels and a lower risk of premature CAD, and gender-specific BMI-R230C interactions were observed for different metabolic traits. These interactions may help explain inconsistencies in associations, and underscore the need to further analyze interactions of this functional and frequent variant with diet, exercise and other environmental factors.

Abnormal high-density lipoproteins in overweight adolescents with atherogenic dyslipidemia.

OBJECTIVE: This study aimed to evaluate high-density lipoprotein functionality and the cardiovascular risk factor profile in the overweight pediatric population. We hypothesized that overweight adolescents with low high-density lipoprotein cholesterol and elevated triglyceride plasma levels have metabolic abnormalities and dysfunctional high-density lipoprotein particles, similar to those reported in adults. PATIENTS AND METHODS: Overweight adolescents with (group 1 [n = 21]) and without (group 2 [n = 36]) atherogenic dyslipidemia (high-density lipoprotein cholesterol: ≤ 40 mg/dL and triglycerides: ≥ 150 mg/dL) and normal-weight normolipidemic subjects, as a reference (group 3 [n = 36]), were included. The cardiovascular risk factor profile (lipids, lipoproteins, high-sensitivity C-reactive protein, and insulin), high-density lipoprotein subclass distribution, composition, and cholesterol efflux capacity were studied. RESULTS: Group 1 adolescents showed abnormalities in high-density lipoprotein subclass distribution and high-density lipoprotein chemical composition, as well as a significantly lower capacity to promote cholesterol efflux (14.8 ± 2.8, 16.5 ± 3.8, 20.4 ± 3.5, for groups 1, 2 and 3, respectively). High-density lipoprotein(2a) (R(2) = 0.212, ß = 0.472, P < .0001) and the Tanner score (R(2) = 0.054, ß = -0.253, P = .02) were the independent predictors of cholesterol efflux. Group 1 also showed a higher degree of cardiovascular abnormalities (an adverse lipoprotein profile, greater insulin resistance and systemic inflammation; and lower low-density lipoprotein size) than group 2, even after BMI and Tanner score adjustment. CONCLUSIONS: This study suggests that atherogenic dyslipidemia identifies overweight adolescents with quantitative, qualitative, and functional high-density lipoprotein abnormalities. Atherogenic dyslipidemia seems to be a marker of an increased risk for developing cardiovascular disease and indicates that those adolescents should be a target of aggressive prevention programs and lipid management guidelines.

High-density lipoprotein subclasses distribution and composition in Mexican adolescents with low HDL cholesterol and/or high triglyceride concentrations, and its association with insulin and C-reactive protein.

We tested whether low high-density lipoprotein cholesterol (HDL-C) and/or high triglycerides are associated to abnormal HDL subclasses distribution and composition, and their relationships with fasting insulin and C-reactive protein (CRP). Four groups of adolescents were studied: group 1 (HDL-C< or =35 mg/dl+TG> or =150 mg/dl; n=16); group 2 (isolated HDL-C< or =35 mg/dl; n=31); group 3 (isolated TG> or =150 mg/dl; n=20); and group 4 (CT<200 mg/dl, HDL-C>35 mg/dl, LDL-C<130 mg/dl, and TG<150 mg/dl; n=39). Tanner score-adjusted proportions of large subspecies (HDL(2b), HDL(2a)) were lower, and small (HDL(3b), HDL(3c)) were higher in groups 1, 2 and 3 than in group 4. As a result, HDL particle size in the three dyslipidemic groups was smaller than in group 4 (p<0.001). HDL CE, FC, PL, and apo AI percent contents were lower, whereas HDL TG percent content was higher in groups 1, 2 and 3 compared to group 4. CRP median values were also significantly higher in the three groups with dyslipidemia than in normolipidemic subjects (group 4). Fasting Insulin concentration and HOMA-IR were significantly higher in group 1 than in the other three groups. In stepwise multivariate analysis HDL subclass distribution and composition were independently associated only with HDL-C and waist circumference. As reported in adults, adolescents with low HDL-C and/or high TG have abnormalities in HDL subclasses distribution and lipid composition, which may render their HDL dysfunctional. In addition, these subjects have high CRP and insulin levels suggesting the presence of chronic low-grade inflammation.