Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia.

BACKGROUND: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. METHODS: An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants. RESULTS: LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband's plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. CONCLUSION: Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p.V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.

Ages at Onset of 5 Cardiometabolic Diseases Adjusting for Nonsusceptibility: Implications for the Pathogenesis of Metabolic Syndrome.

To shed light on the etiology of metabolic syndrome development, it is important to understand whether its 5 component disorders follow certain onset sequences. To explore disease progression of the syndrome, we studied the ages at onset of 5 cardiometabolic diseases: abdominal obesity, diabetes, hypertension, hypertriglyceridemia, and hypo-α-lipoproteinemia. In analyzing longitudinal data from the Cardiovascular Disease Risk Factors Two-Township Study (1989-2002) in Taiwan, we adjusted for nonsusceptibility, utilizing the logistic-accelerated failure time location-scale mixture regression models for left-truncated and interval-censored data to simultaneously estimate the associations of township and sex with the susceptibility probability and the age-at-onset distribution of susceptible individuals for each disease. We then validated the onset sequences of 5 cardiometabolic diseases by comparing the overall probability density curves across township-sex strata. Visualization of these curves indicates that women tended to have onsets of abdominal obesity and hypo-α-lipoproteinemia in young adulthood, hypertension and hypertriglyceridemia in middle age, and diabetes later; men tended to have onsets of abdominal obesity, hypo-α-lipoproteinemia, and hypertriglyceridemia in young adulthood, hypertension in middle age, and diabetes later. Different onset patterns of abdominal obesity, hypo-α-lipoproteinemia, and male hypertension were identified between townships. Our proposed method provides a novel strategy for investigating both pathogenesis and preventive measures of complex syndromes.

Impact of hypoalphalipoproteinemia on quality of life in Taiwanese women with central obesity.

PURPOSE: To investigate the relationship between health-related quality of life (HRQoL) and different cutoff value of low level of high-density lipoprotein cholesterol (HDL-C) in Taiwanese women with different definition of obesity. METHODS: Prospective observational study in women with central obesity was conducted in Taipei City Hospital. A total of 572 women were screened at our clinic, and 227 of them with a body mass index ≧27 kg/m2 defined by the Department of Health in Taiwan and weight circumference ≧80 cm were eligible for the study. We defined two groups as group A-low HDL (HDL-C < 40 mg/dL) and group B-high HDL (HDL-C < 50 mg/dL) according to different definition of hypoalphalipoproteinemia in obese women. RESULTS: Significantly reduced HRQoL score was noted in group A-low HDL compared to group A-high HDL (HDL-C ≧ 40 mg/dL), but not between group B-low HDL and group B-high HDL (HDL-C ≧ 50 mg/dL). Positively correlation was noted between HDL-C level and physical domain of HRQoL score. HDL-C contributes independently to physical domain of HRQoL score after controlling for other factors. Decreased leptin and adiponectin level were noted in hypoalphalipoproteinemia groups. CONCLUSION: Taiwanese obese women with hypoalphalipoproteinemia have adverse impact on HRQoL, especially when the HDL-C level is lower than 40 mg/dL. Both hypoalphalipoproteinemia and hypertension accounted for a great variance to lower scores of physical domain of HRQoL with positively correlation with HDL-C level observed. Decreased leptin and adiponectin were also observed in hypoalphalipoproteinemia group, which implied increased cardiovascular risk. HDL-C level may deem as another indicator for HRQoL in women with central obesity.

The association between periodontitis and dyslipidemia based on the Fourth Korea National Health and Nutrition Examination Survey.

AIMS: The aim of this study was to examine whether dyslipidemia is associated with periodontitis in a representative sample of Korean adults who were involved in the Fourth Korea National Health and Nutrition Examination Survey (KNHANES). MATERIALS AND METHODS: A total of 18,210 subjects over 19 years of age who participated in KNHANES were examined. Dyslipidemia is defined according to the definition proposed by the Korean Society of Lipidology and Atherosclerosis. The periodontal status of the patients was assessed by the Community Periodontal Index (CPI). Multivariate logistic regression analysis was carried out and adjusted for socio-demographics, oral health behaviours and status and general health behaviour. All analyses considered a complex sampling design, and multivariate analysis was also performed in the subgroups (age, gender and current smoking status). RESULTS: Multivariate logistic regression analysis revealed significant associations between dyslipidemia except pre-hypercholesterolemia and periodontitis. In the subgroup analysis, periodontitis was significantly associated with hypo-HDL-cholesterolemia and had a potential association with hyper- triglycerides (TG) in subjects younger than 40 years. The adjusted ORs were greater in the present smoker group than the non-smoker group. CONCLUSIONS: Dyslipidemia except pre-hypercholesterolemia is associated with periodontitis.

Cardiometabolic risk factors and quality of life in severely obese children and adolescents in The Netherlands.

BACKGROUND: The prevalence of severe obesity in children and adolescents is increasing. However, little is known about cardiometabolic risk factors and quality of life of children with severe obesity.Therefore, the aim of this study was to assess the demographic characteristics and the prevalence of cardiometabolic risk factors and quality of life in severely obese children and adolescents undergoing intensive inpatient treatment for obesity. METHODS: Data were collected between August 2009 and April 2011 on 16 children (8-13y) and 64 adolescents (13-19y) with severe obesity (SDS-BMI >= 3.0 or SDS-BMI >= 2.3 and comorbidity) participating in an RCT evaluating two intensive inpatient treatment programs for obesity. Demographic, anthropometric, clinical characteristics and two components of the EuroQol for the assessment of quality of life are described. RESULTS: Eighty percent of participants in this study had at least one cardiometabolic risk factor in addition to severe obesity. Low HDL-cholesterol and hypertension were most prevalent (65.0% respectively 31.2%). The highest significant correlations were found between SDS-BMI and SDS-waist circumference, fasting plasma insulin and HOMA-IR (correlation coefficients respectively 0.80, 0.49, and 0.48). With regard to quality of life, the mean utility score of the participants was 0.79 on a scale of 0.0 to 1.0 on the EuroQol questionnaire and their mean individual valuation was 69.1 on a scale of 0 to100. CONCLUSION: Cardiometabolic risk factors are already highly prevalent in this group of severely obese children and adolescents. The score of 69.1 found for quality of life in this study suggests that participants experience important limitations in their quality of life. However, quality of life is not associated with the prevalence of cardiometabolic risk factors. TRIAL REGISTRATION: Netherlands Trial Register (NTR1678, registered 20-Feb-2009).

[Tocilizumab impact on blood cholesterine transport and early manifestation of atherosclerosis in patients with rheumatoid arthritis].

AIM: To evaluate tocilizumab (TLZ) effects on blood lipids composition and severity of carotid arteries (CA) atherosclerosis in rheumatoid arthritis (RA) patients after 24 week TLZ treatment. MATERIAL AND METHODS: Before and 24 weeks after TLZ treatment 43 RA patients (33 women and 10 men) were examined by DAS 28 index, for blood serum concentration of cholesterol, triglycerides (TG), LPHD and LPLD cholesterol. The drug was injected intravenously in drops in a dose 8 mg/kg each 4 weeks. RESULTS: A 24 week TLZ treatment produced satisfactory and good anti-inflammatory effects in RA patients. Hypoalphalipoproteinemia incidence and atherogenicity index (AI) reduced 3 and 5 times, respectively (p < 0.05). Elevated levels of cholesterol, TG, LDPL cholesterol occurred with the same frequency before and after TLZ treatment. Cholesterol rose by 11.6%, LPHD cholesterol--by 48.9%, TG lowered by 7%, Al--by 31.9% (p < 0.05). LDLP cholesterol decreased Blood lipids composition shifts were associated with marked reduction in the disease activity: decreased concentration of C-reactive protein, IgM rheumatoid factor, DAS28 index, improvement of the patient functional status. Maximal thickness of the intima-media complex of CA increased by 8.2%. Atherosclerotic plaques were revealed before and after treatment in 17 (41.4%) patients from 41, in 5 (12.2%) patients the plaques arose after 6 months and in 5 (12.2%) patients the number of plaques increased. CONCLUSION: Because of both positive and negative effects of IL-6 receptor inhibitors on blood lipids, combined treatment of RA must include statins for correction of dyslipidemia.

Prevalence of dyslipidemias in the Mexican National Health and Nutrition Survey 2006.

OBJECTIVE: To describe the prevalence of lipid abnormalities found in the Mexican National Health and Nutrition Survey 2006 (ENSANut 2006). MATERIAL AND METHODS: Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9- to 12-hour fast. RESULTS: Median lipid concentrations were: cholesterol 198.5 mg/dl, triglycerides 139.6 mg/dl, HDL-cholesterol 39.0 mg/dl, non-HDL-cholesterol 159.5 mg/dl and LDL-cholesterol 131.5 mg/dl. The most frequent abnormality was HDL-cholesterol below 40 mg/dl with a prevalence of 60.5% (95%CI 58.2-62.8%). Hypercholesterolemia (> 200 mg/dl) had a frequency of abnormality of 43.6% (95%CI 41.4-46.0%). Only 8.6% of the hypercholesterolemic subjects knew their diagnosis. Hypertriglyceridemia (>or= 150 mg/dl) was observed in 31.5% (IC 95% 29.3-33.9%) of the population. CONCLUSIONS: The ENSANUT 2006 data confirm that the prevalence of hypoalphalipoproteinemia and other forms of dyslipidemia in Mexican adults is very high.

Association of Severity of Lower Extremity Arterial Disease and Overactive Bladder Syndrome: A Cross Sectional Study.

PURPOSE: The aim of this study aim is to clarify the relationship between Overactive bladder syndrome (OAB) and severity of lower extremity ischemia by using Fontaine classification system. MATERIALS AND METHODS: Patients who were diagnosed with lower extremity arterial disease were enrolled into the study. The Fontaine score of each patient was taken and all patients completed the validated Turkish version of OAB-V8 questionnaire. Body mass index, serum creatinine, blood urea nitrogen, cholesterol and fasting plasma glucose levels were measured. The patients were divided into two groups. Patients with OAB-V8 score above 8 were enrolled into group 1 and patients with OAB-V8 score under 8 were enrolled into group 2. RESULTS: At the end of study period, 181 patients who met the  inclusion criteria were enrolled into the study.  Patients with OAB ? 8 score (n= 79) were compared with  patients with OAB < 8 score (n= 102). The mean age and the mean BMI were significantly higher in patients with OAB ? 8 (P = .001 and P = .001, respectively). Also, HDL- cholesterol level was found significantly lower in group 1 patients  (P= .001). Multivariate regression analysis showed that presence of Fontaine score ? class 2b, age ? 60 years, BMI ? 30 kg/m2 , and HDL-cholesterol levels < 60 mg/dL were predictive factors for OAB. CONCLUSION: The present study  demonstrated that incidence of OAB is higher in patients with severe lower extremity ischemic symptoms, older age, high BMI, and lower HDL-cholesterol level.

Low high-density lipoprotein and increased risk of several cancers: 2 population-based cohort studies including 116,728 individuals.

BACKGROUND: Increasing evidence suggests that high-density lipoprotein (HDL) may play a role in cancer development. We tested the hypothesis that low HDL levels are associated with increased risk of cancer. METHODS: Individuals from two population-based cohorts, the Copenhagen General Population Study (2003-2015, N = 107 341), and the Copenhagen City Heart Study (1991-1994, N = 9387) were followed prospectively until end of 2016 to assess low plasma HDL cholesterol and apolipoprotein A1 as risk factors for cancer using Cox proportional hazard regression. RESULTS: During up to 25 years follow-up, we observed 8748 cancers in the Copenhagen General Population Study and 2164 in the Copenhagen City Heart Study. In the Copenhagen General Population Study and compared to individuals with HDL cholesterol ≥ 2.0 mmol/L (≥ 77 mg/dL), multivariable adjusted hazard ratios (HRs) for any cancer were 1.13 (95% confidence interval 1.04-1.22) for individuals with HDL cholesterol of 1.5-1.99 mmol/L (58-77 mg/dL), 1.18 (1.08-1.30) for HDL cholesterol of 1.0-1.49 mmol/L (39-58 mg/dL), and 1.29 (1.12-1.48) for individuals with HDL cholesterol < 1.0 mmol/L (< 39 mg/dL). Correspondingly, compared to individuals with apolipoprotein A1 ≥ 190 mg/dL, HRs for any cancer were 1.06 (0.96-1.17) for individuals with apolipoprotein A1 of 160-189 mg/dL, 1.18 (1.07-1.30) for apolipoprotein A1 of 130-159 mg/dL, and 1.28 (1.13-1.46) for individuals with apolipoprotein A1 < 130 mg/dL. Among 27 cancer types, low HDL cholesterol and/or apolipoprotein A1 were associated with increased risk of multiple myeloma, myeloproliferative neoplasm, non-Hodgkin lymphoma, breast cancer, lung cancer, and nervous system cancer. Results were overall similar in women and men separately, and in the Copenhagen City Heart Study. CONCLUSIONS: Low HDL levels were associated with increased risk of several cancers. Increased risk was most pronounced for hematological and nervous system cancer, and to a minor extent for breast and respiratory cancer.

No evidence of increased risk for certain highly atherogenic lipoprotein phenotypes in HIV-infected patients.

BACKGROUND: There is a need to assess whether human immunodeficiency virus (HIV)-infected patients are more likely than noninfected individuals to have any of the specific lipoprotein combination profiles identified as the best predictors of future cardiovascular disease in the general population. METHODS: One hundred five infected patients, randomly selected from a Mexican HIV clinic, and 105 age- and gender-matched noninfected community volunteers, were enrolled to study the prevalence of each of three highly atherogenic lipoprotein phenotypes [high apolipoprotein (Apo)B/ApoA-I ratio, hypertriglyceridemia with high ApoB and hypoalphalipoproteinemia with high ApoB], and the relationship between time of exposure to antiretroviral therapy (ART) drug class and lipid changes. RESULTS: The highly atherogenic lipoprotein phenotypes were similarly frequent in both groups. There was a nonsignificant increased risk of dyslipidemia with longer exposure to any of the ART drug classes, although this hazard seems to be greater in patients with central fat accumulation. CONCLUSIONS: No evidence of increased risk for certain highly atherogenic lipoprotein phenotypes in HIV-infected patients was found. More than one pathogenic mechanism for ART-associated dyslipidemia is postulated.

[Dyslipidemia prevalence and its relationship with insulin resistance in a population of apparently healthy subjects]. / Prevalencia de dislipidemias en una población de sujetos en apariencia sanos y su relación con la resistencia a la insulina.

OBJECTIVE: Evaluate dyslipidemia prevalence and its association with insulin resistance in a cohort of apparently healthy subjects. MATERIAL AND METHODS: A cross-sectional study was conducted with 1,179 donors ages 35 to 65 years. The sample population was comprised of 71% men, with an average age of 44 +/- 7. Clinical records, anthropometric data, lipid profile, fasting glycaemia, and insulin levels were obtained. RESULTS: Prevalence of hypertriglyceridemia was 57.3%, C-HDL under normal limits was 52.4%, and hypercholesterolemia was 48.7%. In addition, 36.8% of the obese individuals (as measured by waist perimeter) had hypertriglyceridemia/hypoalphalipoproteinemia, 35.2% had mixed dyslipidemia, and 33.4% had hypertriglyceridemia. Patterns of dyslipidemia were higher in subjects diagnosed with insulin resistance. CONCLUSIONS: Insulin resistance associated with hypertriglyceridemia and hypoalphalipoproteinemia was common among our studied population. However, a significant proportion of cases of apparent healthy individuals continue to go undiagnosed.

Low serum HDL-cholesterol concentrations in mid-life predict late-life cognitive impairment in type 2 diabetes: The Fremantle diabetes study.

In a study involving patients with type 2 diabetes assessed annually over 5years, serum HDL-cholesterol was the sole mid-life metabolic predictor of late-life cognitive impairment.

Functional mutations of the ABCA1 gene in subjects of French-Canadian descent with HDL deficiency.

Mutations in the ABCA1 gene cause defective cellular lipid efflux and severe familial HDL deficiency. We examined the prevalence of mutations at the ABCA1 gene in 58 unrelated probands of French-Canadian descent with HDL deficiency (HDL-C<5th percentile). A defective cellular cholesterol or phospholipid efflux (<75% and <70% of normal controls, respectively) was identified in 14/58 (24%) of subjects. Using direct sequencing of the ABCA1 gene, we found mutations in 12/58 ( approximately 20%) of subjects. Four probands were previously identified with diverse ABCA1 gene defects. However, we identified a novel frameshift mutation (F1840L, L1869X); a proband was heteroallelic for the N1800H mutation, previously reported in a case of Tangier disease, and a novel missense mutation (Q2210H); a novel variant (G616V), predicted to impart a functional defect in the protein, was also found in another proband. Three probands had the S1731C mutation, while two others had the R1851X and K776N documented mutations, respectively. Taken together, these data suggest that approximately 20% of French-Canadian patients with severe HDL deficiency are associated with a defective ABCA1. Interestingly, in two families studied, mutations in the ABCA1 gene did not segregate with the lipid efflux defect, suggesting that other proteins are involved in the ABCA1-mediated cellular lipid efflux.

Clustering of cardiometabolic risk factors and risk of elevated HbA1c in non-Hispanic White, non-Hispanic Black and Mexican-American adults with type 2 diabetes.

AIM: To determine which cardiometabolic risk factors and clusters of cardiometabolic risk factors that are mostly associated with elevated HbA1c in non-Hispanic White (NHW), non-Hispanic Black (NHB) and Mexican-American (MA) adults who have type 2 diabetes. METHODS: Data (n=2910) from the United States National Health and Nutritional Examination Surveys were used in this study. Elevated HbA1c was defined as having HbA1c value was 7% or greater. Race/ethnicity-specific associations of individual and clustered (2-5 factors) cardiometabolic risk factors with elevated HbA1c were determined using prevalence odds ratio from multivariate logistic regression analyses. Statistical adjustments were made for sex, age, education, income and marital status. RESULTS: Joint occurrence of abdominal obesity, high blood pressure, and elevated triglycerides and joint occurrence of high blood pressure, elevated triglycerides and low HDL were more highly associated with elevated odds of HbA1c compared to other cardiometabolic risk factors joint occurrences. Joint occurrences of abdominal obesity, high blood pressure, and elevated triglycerides was associated with 2.3 (95% CI: 1.2-3.3), 9.1 (95% CI: 2.9-28.7) and 4.8 (95% CI: 2.0-11.5) increased odds of elevated HbA1c in NHW, NHB and MA, respectively. The corresponding values for the joint occurrence of high blood pressure, elevated triglycerides and low HDL was associated with 2.4 (95% CI: 1.2-3.7), 3.5 (95% CI: 1.1-5.5) and 2.6 (95% CI: 1.5-4.7) increased odds of elevated HbA1c in NHW, NHB and MA, respectively. CONCLUSION: This finding calls for consideration of cardiovascular risk factor clustering in deciding medical therapies to optimize glycemic control in individuals with type 2 diabetes. Interventions designed to achieve glycemic control coupled with modification of cardiometabolic risk factors may be crucial in alleviating sequelae resulting from type 2 diabetes.

[Atherogenic dyslipidemia in patients with type 1 diabetes mellitus]. / Dislipidemia aterogénica en pacientes con diabetes mellitus tipo 1.

BACKGROUND AND OBJECTIVE: To assess the prevalence of lipid abnormalities, with special emphasis on atherogenic dyslipidemia and its relationship with chronic complications in patients with type 1 diabetes mellitus (T1DM). PATIENTS AND METHOD: Cross-sectional study including all patients aged 18 and over, diagnosed of T1DM attending the outpatient clinic at Hospital del Mar and Hospital de Granollers, in Barcelona, during 2008. RESULTS: Of the 291 enrolled patients, 17.2 and 7.9% had high density lipoproteins (HDL) cholesterol<40 mg/dL (men) or<50mg/dL (women) and triglycerides>150 mg/dL, respectively. Hypoalphalipoproteinemic patients had a higher prevalence of peripheral neuropathy (28 vs. 7.1%, P<.001), macroalbuminuria (14 vs. 2.5%, P<.001) and higher concentrations of triglycerides (107.5 [55.8] vs. 82.7 [36] mg/dL, P<.0001) compared with those with normal/high HDL cholesterol levels. Hypertriglyceridemia was associated with increasing age (43.6 [11.2] vs. 37.6 [11.8] yr, P<.02), higher prevalence of hypertension (47.8 vs. 22.8%, P<.008), metabolic syndrome (82.6 vs. 22%, P<.001) and microangiopathic complications, lower insulin sensitivity (6.75 [2.1] vs. 8.54 [2.6] mg/Kg(-1)/min(-1), P<.004) compared with the normotriglyceridemic group. CONCLUSION: One in 5 patients with T1DM has hypoalphalipoproteinemia or hypertriglyceridemia and these conditions are associated with 3 fold-increase microangiopathy. Thus, in these patients glycemic and blood pressure but also lipid profile control must be optimum.

Clustering and combining pattern of metabolic syndrome components in a rural Brazilian adult population.

CONTEXT AND OBJECTIVE Metabolic syndrome is characterized by clustering of cardiovascular risk factors such as obesity, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance and arterial hypertension. The aim of this study was to estimate the probability of clustering and the combination pattern of three or more metabolic syndrome components in a rural Brazilian adult population. DESIGN AND SETTING This was a cross-sectional study conducted in two rural communities located in the Jequitinhonha Valley, Minas Gerais, Brazil. METHODS The sample was composed of 534 adults (both sexes). Waist circumference, blood pressure and demographic, lifestyle and biochemical characteristics were assessed. The prevalences of metabolic syndrome and its components were estimated using the definitions of the National Cholesterol Education Program - Adult Treatment Panel III. A binomial distribution equation was used to evaluate the probability of clustering of metabolic syndrome components. The statistical significance level was set at 5% (P < 0.05). RESULTS Metabolic syndrome was more frequent among women (23.3%) than among men (6.5%). Clustering of three or more metabolic syndrome components was greater than expected by chance. The commonest combinations of three metabolic syndrome components were: hypertriglyceridemia + low levels of HDL-c + arterial hypertension and abdominal obesity + low levels of HDL-c + arterial hypertension; and of four metabolic syndrome components: abdominal obesity + hypertriglyceridemia + low levels of HDL-c + arterial hypertension. CONCLUSION The population studied presented high prevalence of metabolic syndrome among women and clustering of its components greater than expected by chance, suggesting that the combination pattern was non-random.

Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes).

OBJECTIVES: This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial. BACKGROUND: Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. METHODS: Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. RESULTS: Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. CONCLUSIONS: Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.

[Diagnostic criteria for hypoalphalipoproteinemia and the threshold associated with cardiovascular protection in a Mexican Mestizo population]. / Criterio diagnóstico para hipoalfalipoproteinemia y punto de corte asociado con protección cardiovascular en una población mestiza mexicana.

BACKGROUND AND OBJECTIVES: In the Mexican Mestizo and Indian populations it is unknown the diagnostic criteria (DC) and associated risk of myocardial infarction (MI) for the HDL-cholesterol (HDL-c). We aimed to establish, in a Mexican adult population without cardiovascular risk factors, their HDL-c concentrations, the DC for hypoalphalipoproteinemia and prevalence base on the percentile-10 and the risk associated with MI, as well as the threshold (TH) associated with cardiovascular protection. SUBJECTS AND METHODS: In 826 adult Mestizos, 98 Indians and 155 Mestizos with MI for the first time the average HDL-c serum concentrations were determined. Then the percentile and statistical analysis were carried out. RESULTS: The average HDL-c (mg/dl) concentrations for Mestizos and Indians were 43.2 and 37.2 and the ones inferior to the percentile-10 were <30 and <26, respectively. In Mestizos, HDL-c concentrations of ≤ 35 mg/dl (odds ratio [OR] 1.91, 95% confidence interval [95%CI] 1.3-2.8, P=.001) were associated with MI and those >35 (OR 0.52, IC 95% 0.36-0.76, P=.001) were associated with a cardiovascular protection of 52%. The hypoalphalipoproteinemia prevalences in Mestizos and Indians were: for the percentile-10 DC 9 and 11% and for the TH associated with MI ≤ 35, 26 and 54%, respectively. CONCLUSIONS: The Indians average HDL-c concentration was significantly lower (P<.003) than for Mestizos. The established DC showed that the hypoalphalipoproteinemia prevalences in both populations were similar to those for other open populations. In Mestizos, HDL-c concentrations > 35 mg/dl are protective for MI, but it will be necessary to establish this TH for the Indian population. Each population should establish its own DC for hypoalphalipoproteinemia.

Lipid profile of schoolchildren from Recife, PE.

BACKGROUND: The occurrence of dyslipidemia is increasing in pediatric populations. Altered lipid profiles are related to a higher incidence of hypertension and atherosclerotic disease. OBJECTIVE: To evaluate the extent of dyslipidemia and investigate its association with overweight and abdominal obesity in adolescent students from Recife, Brazil. METHODS: Personal data, socioeconomic level, anthropometric measurements and lipid profile of 470 adolescents, aged 10 to 14 years, of both sexes, students at the Public School system in the city of Recife, state of Pernambuco, Brazil, were obtained. The statistical analysis was carried out using the Epi-info 6.04 and SPSS 13.0 software. The level of significance was set at 5%. RESULTS: The majority of the population was dyslipidemic (63.8%; 95%CI: 59.3 - 68.2), with hypoalphalipoproteinemia being the most prevalent dyslipidemia (56%; 95%CI: 51.3 - 60.5). Adolescents who were overweight or who had abdominal obesity presented higher levels of triglycerides and lower levels of HDL-cholesterol (p < 0.05). Levels of total cholesterol and fractions were not different between sexes. CONCLUSION: A high incidence of unfavorable lipid profile was shown in this series, demonstrating the necessity to measure the lipid profile as early as this age range. Healthy lifestyle measures should be encouraged in this population.

Niacin and fibrate use among patients with high triglycerides and low high-density lipoprotein cholesterol.

BACKGROUND: National guidelines recommend treating low HDL and/or high triglycerides (TG) with adjunctive therapy that supplements statin monotherapy in patients with multiple cardiovascular disease (CVD) risk factors. Niacin and fibrates have been shown in clinical trials to be effective as adjunctive therapy for these lipid abnormalities. OBJECTIVE: To evaluate the pharmacologic treatment of low HDL and high TG in real-world practice by assessing a large managed-care population with CVD risk factors enrolled in a commercial health plan. RESEARCH DESIGN AND METHODS: Complete lipid panel results (LDL, HDL, TG) obtained between 1/1/2006 and 12/31/2006 (index lab) were available for all participants. Subjects were observed 180 days pre-index to determine which CVD risk factors were present (male aged 45+, female 55+, coronary heart disease, hypertension, diabetes mellitus). Patients whose LDL was at goal but who had low HDL and high TG were assessed for lipid treatment status by evaluating outpatient pharmacy claims 6 months pre- and post-index. RESULTS: Treatment with any lipid therapy increased for all risk groups, and by total risk factors, from pre-index to post-index. Use of fibrates and niacin, alone or in combination with a statin, also increased for all risk groups, and by total risk factors as well, but was below expectations based on guideline recommendations. For example, among patients with 4 risk factors, <20% of patients with low HDL/high TG received niacin and/or a fibrate post-index date. CONCLUSIONS: Our results indicate that in actual clinical practice, niacin and fibrates are underutilized in the treatment of low HDL and high TG. The findings of this study must be considered within the limitations of database analysis as claims data are collected for the purpose of payment and not research.