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.

Adipose tissue dysfunction increases fatty liver association with pre diabetes and newly diagnosed type 2 diabetes mellitus.

BACKGROUND: To evaluate the role of adipose tissue function on the association of fatty liver (FL) with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes mellitus (nT2D). METHODS: In 1264 subjects, computed tomography was used to evaluate FL and elevated visceral adipose tissue (VAT). Fasting plasma glucose, <5.6, 5.6-6.9 and ≥7 mmol/l, were used to defined normoglycemic (NG), IFG or nT2D, respectively. Elevated free fatty acids, low serum adiponectin levels and adipose tissue insulin resistance (Adipo-IR), were used as markers of adipose tissue dysfunction. RESULTS: Compared to NG subjects, those with IFG or nT2D had higher prevalence of FL and elevated VAT. FL was found to be independently associated with IFG and nT2D. Adipo-IR increased the association between FL and IFG [OR: 2.46 (95% I.C.: 1.73-3.49) to 5.42 (3.11-9.41)], whereas low adiponectin levels had a higher effect on the FL and nT2D association [OR: 4.26 (2.18-8.34) to 8.53 (2.96-24.55)]. CONCLUSION: Fatty liver was independently associated with IFG and nT2D. Our results indicate for the first time, that adipose tissue dysfunction increases these associations.

Cholesterol efflux and metabolic abnormalities associated with low high-density-lipoprotein-cholesterol and high triglycerides in statin-treated coronary men with low-density lipoprotein-cholesterol <70 mg/dl.

In 69 statin-treated male coronary patients with low-density lipoprotein cholesterol at goal levels (<70 mg/dl), the investigators tested whether low high-density lipoprotein (HDL) cholesterol (<40 mg/dl) and high triglyceride (>150 mg/dl) are associated with dysfunctional HDL particles and abnormal insulin, adiponectin, C-reactive protein serum levels. Thirty-four patients with low HDL cholesterol and high triglyceride (dyslipidemia) and 35 patients with low-density lipoprotein cholesterol, HDL cholesterol, and triglyceride at target levels (normolipidemia) were studied. Twenty healthy men were also studied. High-sensitivity C-reactive protein was measured using immunonephelometry, insulin using a radioimmunometric assay, and total adiponectin by enzyme-linked immunosorbent assay. Cell cholesterol efflux to serum and total isolated HDL was assayed using rat hepatoma Fu5AH cells for scavenger receptor class B type 1-mediated efflux. Compared to the normolipidemia and healthy groups, and after adjustment for age and waist circumference, patients with dyslipidemia showed higher fasting insulin (14, 9.9, and 8.5 µU/ml, respectively), homeostasis model assessment of insulin resistance values (3.4, 2.3, and 1.8, respectively), lower adiponectin concentrations (5.1, 8.1, and 11 µg/ml, respectively), and reduced cholesterol efflux to serum (14%, 15%, and 19%, respectively) and to HDL fractions (4.4%, 4.6%, and 5.6%, respectively) (p <0.05 for all variables). Multivariate analysis showed that adiponectin and apolipoprotein A1 accounted for 10.7% and 3.9%, respectively, of the variance in cholesterol efflux. In conclusion, the decreased cholesterol efflux and metabolic abnormalities found in the dyslipidemia group may contribute to the residual risk observed in the large statin trials and the higher morbidity and mortality in statin-treated coronary patients with low HDL cholesterol even when attaining low-density lipoprotein cholesterol <70 mg/dl.

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.

[Obesity or overweight and metabolic syndrome in Mexico City teenagers]. / Exceso de peso y síndrome metabólico en adolescentes de la Ciudad de México.

UNLABELLED: aim: To know the metabolic syndrome and its components prevalence in Mexico City adolescents sample. DESIGN: A cross-sectional survey was conducted in 772 men and 1078 women, 12 to 16 years old, from 8 randomly selected public junior high schools in Mexico City. METHODS: Anthropometric variables, lipids, lipoproteins, Apo AI and B, glucose and insulin were determined. RESULTS: Prevalence of metabolic syndrome was 12.5%, 11.15% in men and 13.5% en women (p ns). The most frequently metabolic syndrome component found in México City adolescents was low HDL-C levels (38%), followed by hypertriglyceridemia (25.5%), hypertension (19.2%), central obesity (11.8%) and elevated fasting glucose (1.7). Except by the hypertriglyceridemia, higher in woman than in men, 28.2% vs. 21.6%, p < 0.001, the prevalence of metabolic syndrome components was similar between males and females. CONCLUSIONS: The high prevalence of biochemical and physiological factors of metabolic syndrome, associated with overweight and obesity in Mexico City adolescents, increases the risk of premature development of coronary atherosclerosis and diabetes mellitus in this population.

Exceso de peso y síndrome metabólico en adolescentes de la Ciudad de México / Obesity or overweight and metabolic syndrome in Mexico City teenagers

Objetivo: Conocer la prevalencia del síndrome metabólico y sus componentes en una muestra de adolescentes de la Ciudad de México. Diseño: Se efectuó un estudio transversal en 772 varones y 1,078 mujeres de 12 a 16 años edad, en ocho escuelas secundarias de la Ciudad de México seleccionadas al azar. Métodos: Se realizaron medidas antropométricas, lípidos y lipoproteínas, Apo-AI y B, glucosa e insulina. Resultados: La prevalencia del síndrome metabólico fue de 12.5%, 11.5% en los varones y 13.5% en las mujeres (p = ns). La concentración baja de colesterol en las HDL fue el componente del síndrome metabólico más frecuente (38%), seguido de triglicéridos elevados (25.5%), hipertensión arterial (19.2%), obesidad central (11.8%) y glucosa en ayuno elevada (1.7%). Excepto por la hipertrigliceridemia, 28.2% en las mujeres y 21.6% en los varones (p < 0.001), la prevalencia de los componentes del síndrome metabólico fue similar en ambos géneros. Conclusiones: La prevalencia elevada de componentes bioquímicos y fisiológicos del síndrome metabólico, asociada con el sobrepeso y la obesidad en los adolescentes de la Ciudad de México, incrementa el riesgo en este grupo de la población de desarrollar de manera prematura ateroesclerosis coronaria y diabetes mellitus.

Aim: To know the metabolic syndrome and its components prevalence in Mexico City adolescents sample. Design: A cross-sectional survey was conducted in 772 men and 1078 women, 12 to 16 years old, from 8 randomly selected public junior high schools in Mexico City. Methods: Anthropometric variables, lipids, lipoproteins, Apo AI and B, glucose and insulin were determined. Results: Prevalence of metabolic syndrome was 12.5%, 11.15% in men and 13.5% en women (p ns). The most frequently metabolic syndrome component found in México City adolescents was low HDL-C levels (38%), followed by hypertriglyceridemia (25.5%), hypertension (19.2%), central obesity (11.8%) and elevated fasting glucose (1.7). Except by the hypertriglyceridemia, higher in woman than in men, 28.2% vs. 21.6%, p < 0.001, the prevalence of metabolic syndrome components was similar between males and females. Conclusions: The high prevalence of biochemical and physiological factors of metabolic syndrome, associated with overweight and obesity in Mexico City adolescents, increases the risk of premature development of coronary atherosclerosis and diabetes mellitus in this population.

[High and low density lipoprotein abnormalities in coronary patients with LDL-C at target and uncontrolled HDL-C and triglycerides]. / Alteraciones de las lipoproteínas de alta y baja densidad en pacientes coronarios con C-LDL en meta pero C-HDL y triglicéridos anormales.

OBJECTIVE: To investigate the high density lipoprotein (HDL) subclasses distribution and chemical composition, as well as low density lipoprotein (LDL) size and LDL oxidation, in coronary male patients treated with statins, that had LDL-cholesterol levels at target (< 100 mg/dL), but whose HDL-cholesterol (< 40 mg/dL) and triglycerides (TG > or = 150 mg/dL) levels were abnormal. The control group was formed by statin treated coronary male patients with LDL-C below 100 mg/dL and normal HDL-C and TG levels. MATERIAL AND METHODS: HDL subclasses and LDL size were determined by gradient gel electrophoresis. LDL susceptibility to oxidation was determined by measuring lag phase duration, after adding the oxidant agent. RESULTS: Compared with the control group (n = 35), patients with low HDL-C + high TG (n = 34) showed significantly lower proportions of large HDL and higher proportions of small HDL particles. In addition, these patients had abnormal HDL composition, smaller LDL size, and higher LDL susceptibility to oxidation (p < 0.05 for all). CONCLUSIONS: Coronary patients with optimal LDL-C levels on statin therapy but with low HDL-C and high TG, have HDL and LDL abnormalities that have been shown to be associated with a higher risk of new coronary events.

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.

Alteraciones de las lipoproteínas de alta y baja densidad en pacientes coronarios con C-LDL en meta pero C-HDL y triglicéridos anormales / High and low density lipoprotein abnormalities in coronary patients with LDL-C at target and uncontrolled HDL-C and triglycerides

OBJECTIVE: To investigate the high density lipoprotein (HDL) subclasses distribution and chemical composition, as well as low density lipoprotein (LDL) size and LDL oxidation, in coronary male patients treated with statins, that had LDL-cholesterol levels at target (< 100 mg/dL), but whose HDL-cholesterol (< 40 mg/dL) and triglycerides (TG > or = 150 mg/dL) levels were abnormal. The control group was formed by statin treated coronary male patients with LDL-C below 100 mg/dL and normal HDL-C and TG levels. MATERIAL AND METHODS: HDL subclasses and LDL size were determined by gradient gel electrophoresis. LDL susceptibility to oxidation was determined by measuring lag phase duration, after adding the oxidant agent. RESULTS: Compared with the control group (n = 35), patients with low HDL-C + high TG (n = 34) showed significantly lower proportions of large HDL and higher proportions of small HDL particles. In addition, these patients had abnormal HDL composition, smaller LDL size, and higher LDL susceptibility to oxidation (p < 0.05 for all). CONCLUSIONS: Coronary patients with optimal LDL-C levels on statin therapy but with low HDL-C and high TG, have HDL and LDL abnormalities that have been shown to be associated with a higher risk of new coronary events.

Comparison of metformin versus rosiglitazone in patients with Acanthosis nigricans: a pilot study.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition commonly present on the neck of obese subjects. Obesity is often accompanied by insulin resistance and/or hyperinsulinemia. Metformin and rosiglitazone are 2 pharmacologic agents useful in conditions characterized by insulin resistance. OBJECTIVE: The aim of our study was to compare the efficacy of metformin versus rosiglitazone on AN lesions of the neck as well as their effects on metabolic and anthropometric variables. METHODS: This 12-week randomized, open-label pilot study involved overweight or obese subjects with AN treat with either metformin (n=4) or rosiglitazone (n=3). RESULTS: Only the rosiglitazone group showed a significant reduction in insulin levels. No effect on the severity of AN was observed, but modest improvements of skin texture occurred in both treatment groups. CONCLUSIONS: Metformin and rosiglitazone were well-tolerated. Although efficacy on skin lesions was very modest, their use in acanthotic subjects might be useful during longer treatment periods.

Influencia de la administración transdérmica de 17-b estradiol sobre la liberación de hormona de crecimiento mediante la hormona liberadora de la hormona de crecimiento (gh-rh-1-29) en mujeres climatéricas pre y postratamiento / Influence of transdermal 17-ß estradiol administration on growth hormones secretion in menopausal women before and after treatment under the stimulus of growth hormonereasing hormone (GH-RH)

Antecedentes. En la actualidad se ha generado gran interés en el papel que juega la disminución de la hormona liberadora de la hormona de crecimiento y la hormona de crecimiento y su repercusión en varias partes del organismo como factores responsables de los cambios observados en la mujer climatérica, en especial en el sistema nervioso central, cardiovascular, genitourinario, digestivo y osteomuscular. Objetivo. Evaluar la influencia de la administración transdérmica de 17-b estradiol sobre la liberación de la hormona de crecimiento en mujeres climatéricas pre y postratamiento mediante la administración de la hormona liberadora de la hormona de crecimiento. Material y método. Se incluyeron cinco pacientes con edad promedio de 51 ñ 4.1 años, con cuadro clínico y bioquímico de climaterio. Tiempo de evolución: 5.4 ñ 4.61 (rango: 1-13 años). Se monitorizó la pulsatilidad de la hormona de crecimiento durante los primeros 120 minutos y tres horas más después de la administración de la hormona liberadora de la hormona de crecimiento (GH-RH-1-29-NH2), I.V. en bolo (50 µg). La obtención del suero para determinar la hormona de crecimiento se realizó cada 15 minutos antes y después del estímulo. Inmediatamente después se inició la sustitución hormonal con el 17-b estradiol transdérmico (parches de 50 µg) dos veces por semana. La evaluación clínica y el estudio mediante la estimulación con GH-RH-1-29 se realizaron al tiempo 0 (basal), 1, 3 y 6 meses de iniciado el tratamiento con las mismas condiciones descritas previamente. Resultados. La pulsatilidad de la hormona de crecimiento antes de iniciada la sustitución estrogénica en los cinco pacientes fue de: X:0.48 ñ 0.22; 0.38 ñ 0.17; 0.45 ñ 0.25 y 0.69 ñ 0.29 (Basal, 1, 3 y 6 meses, respectivamente) y de 2.74 ñ 1.21; 3.48 ñ 1.32 (p > 0.05); 4.91 ñ 1.57 (p < 0.05) y 6.04 ñ 1.69 (p < 0.05) (p en relación con la basal) postestímulo con GH-RH-1-29, Basal, 1, 3 y 6 meses, respectivamente, postestrogenoterapia transdérmica. Los niveles basales de gonadotrofinas descendieron de 54.68 ñ 27 a 33.20 ñ 11.23 y de 40.48 ñ 12 a 28.30 ñ 6.70 (FSH y LH, respectivamente, pre y postratamiento) y los valores basales de estradiol se incrementaron de 1.82 ñ 4.06 a 25.95 ñ 5.96 después de iniciada la estrogenoterapia