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Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease.
Boden, WE, Miller, MG, McBride, R, Harvey, C, Snabes, MC, Schmidt, J, McGovern, ME, Fleg, JL, Desvigne-Nickens, P, Anderson, T, et al
American heart journal. 2020;:65-76
Abstract
BACKGROUND Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.
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Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis.
Gunning, MN, Sir Petermann, T, Crisosto, N, van Rijn, BB, de Wilde, MA, Christ, JP, Uiterwaal, CSPM, de Jager, W, Eijkemans, MJC, Kunselman, AR, et al
Human reproduction update. 2020;(1):103-117
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Abstract
BACKGROUND Women diagnosed with polycystic ovary syndrome (PCOS) suffer from an unfavorable cardiometabolic risk profile, which is already established by child-bearing age. OBJECTIVE AND RATIONALE The aim of this systematic review along with an individual participant data meta-analysis is to evaluate whether cardiometabolic features in the offspring (females and males aged 1-18 years) of women with PCOS (OPCOS) are less favorable compared to the offspring of healthy controls. SEARCH METHODS PubMed, Embase and gray literature databases were searched by three authors independently (M.N.G., M.A.W and J.C.) (last updated on 1 February 2018). Relevant key terms such as 'offspring' and 'PCOS' were combined. Outcomes were age-specific standardized scores of various cardiometabolic parameters: BMI, blood pressure, glucose, insulin, lipid profile and the sum scores of various cardiometabolic features (metabolic sum score). Linear mixed models were used for analyses with standardized beta (β) as outcome. OUTCOMES Nine relevant observational studies could be identified, which jointly included 1367 children: OPCOS and controls, originating from the Netherlands, Chile and the USA. After excluding neonates, duplicate records and follow-up screenings, a total of 885 subjects remained. In adjusted analyses, we observed that OPCOS (n = 298) exhibited increased plasma levels of fasting insulin (β = 0.21(95%CI: 0.01-0.41), P = 0.05), insulin-resistance (β = 0.21(95%CI: 0.01-0.42), P = 0.04), triglycerides (β = 0.19(95%CI: 0.02-0.36), P = 0.03) and high-density lipoprotein (HDL)-cholesterol concentrations (β = 0.31(95%CI: 0.08-0.54), P < 0.01), but a reduced birthweight (β = -116(95%CI: -195 to 38), P < 0.01) compared to controls (n = 587). After correction for multiple testing, however, differences in insulin and triglycerides lost their statistical significance. Interaction tests for sex revealed differences between males and females when comparing OPCOS versus controls. A higher 2-hour fasting insulin was observed among female OPCOS versus female controls (estimated difference for females (βf) = 0.45(95%CI: 0.07 to 0.83)) compared to the estimated difference between males ((βm) = -0.20(95%CI: -0.58 to 0.19)), with interaction-test: P = 0.03. Low-density lipoprotein-cholesterol differences in OPCOS versus controls were lower among females (βf = -0.39(95%CI: -0.62 to 0.16)), but comparable between male OPCOS and male controls (βm = 0.27(95%CI: -0.03 to 0.57)), with interaction-test: P < 0.01. Total cholesterol differences in OPCOS versus controls were also lower in females compared to the difference in male OPCOS and male controls (βf = -0.31(95%CI: -0.57 to 0.06), βm = 0.28(95%CI: -0.01 to 0.56), interaction-test: P = 0.01). The difference in HDL-cholesterol among female OPCOS versus controls (βf = 0.53(95%CI: 0.18-0.88)) was larger compared to the estimated mean difference among OPCOS males and the male controls (βm = 0.13(95%CI: -0.05-0.31), interaction-test: P < 0.01). Interaction test in metabolic sum score revealed a significant difference between females (OPCOS versus controls) and males (OPCOS versus controls); however, sub analyses performed in both sexes separately did not reveal a difference among females (OPCOS versus controls: βf = -0.14(95%CI: -1.05 to 0.77)) or males (OPCOS versus controls: βm = 0.85(95%CI: -0.10 to 1.79)), with P-value < 0.01. WIDER IMPLICATIONS We observed subtle signs of altered cardiometabolic health in OPCOS. Therefore, the unfavorable cardiovascular profile of women with PCOS at childbearing age may-next to a genetic predisposition-influence the health of their offspring. Sensitivity analyses revealed that these differences were predominantly observed among female offspring aged between 1 and 18 years. Moreover, studies with minimal risk of bias should elucidate the influence of a PCOS diagnosis in mothers on both sexes during fetal development and subsequently during childhood.
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Association between Rosacea and Cardiovascular Diseases and Related Risk Factors: A Systematic Review and Meta-Analysis.
Li, Y, Guo, L, Hao, D, Li, X, Wang, Y, Jiang, X
BioMed research international. 2020;:7015249
Abstract
BACKGROUND Rosacea is a common inflammatory skin disorder. Several studies, but not all, have suggested a high prevalence of cardiovascular diseases (CVDs) in rosacea patients. This study is aimed at investigating the association between rosacea and CVDs and related risk factors. METHODS We performed a literature search through PubMed, Embase, and Web of Science databases, from their respective inception to December 21, 2019. Two reviewers independently screened the articles, extracted data, and performed analysis, following the PRISMA guidelines. Odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes. The included studies' quality was evaluated using the Newcastle Ottawa Scale (NOS). RESULTS The final meta-analysis included ten studies. The pooled analysis found no association between rosacea prevalence and the incidence of CVDs (OR 0.97; 95% CI 0.86-1.10). Rosacea was found to be significantly associated with several risk factors for CVDs (OR 1.17; 95% CI 1.05-1.31), including hypertension (OR 1.17; 95% CI 1.02-1.35), dyslipidemia (OR 1.34; 95% CI 1.00-1.79), and metabolic syndrome (OR 1.72; 95% CI 1.09-2.72). However, no association was found between rosacea and diabetes mellitus (OR 0.98; 95% CI 0.82-1.16). Among the biological parameters, a significant association was found between rosacea and total cholesterol (SMD = 0.40; 95% CI = -0.00, 0.81; p < 0.05), low-density lipoprotein cholesterol (SMD = 0.28; 95% CI = 0.01, 0.56; p < 0.05), and C-reactive protein (CRP) (SMD = 0.25; 95% CI = 0.10, 0.41; p < 0.05). We found no association between rosacea and high-density lipoprotein cholesterol (SMD = 0.00; 95% CI = -0.18, 0.18; p = 0.968) or triglycerides (SMD = 0.10; 95% CI = -0.04, 0.24; p = 0.171). CONCLUSIONS Although no significant association was found between rosacea and CVDs, rosacea was found to be associated with several of related risk factors. Patients with rosacea should pay more attention to identifiable CVD risk factors, especially those related to inflammatory and metabolic disorders.
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Maternal plasma cholesterol concentration and preterm birth: a meta-analysis and systematic review of literature.
Welge, JA, Warshak, CR, Woollett, LA
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;(13):2291-2299
Abstract
Background: Women that previously had preterm labor are at an increased risk for heart disease. Because spontaneous preterm birth is an adverse pregnancy outcome that affects millions of children worldwide, our objective was to review and analyze studies that have examined associations between maternal total cholesterol (TC), LDL-C, and HDL-C concentrations during pregnancy and the risk of preterm birth to potentially define biomarkers or targets for treatment.Method: A search was performed and 22 articles were found that examined the association of maternal plasma cholesterol concentrations and preterm birth. A meta-analysis was performed on 10 of the articles, those that used maternal lipid concentrations as the outcome and presented results as means plus variables, and a qualitative review was performed on all 22 articles.Results: The meta-analysis showed no relationship between maternal TC, LDL-C, or HDL-C and increased risk of preterm birth, although, a near significant relationship between low maternal HDL-C concentration and preterm birth (p = .055). Importantly, associations increased when cholesterol concentrations were combined with inflammatory markers or metabolic syndrome factors.Conclusions: The relationship between maternal cholesterol levels and preterm birth is heterogeneous. Associations are strengthened when maternal cholesterol concentrations are combined with other factors that may be related to more recently defined lipoprotein functions.
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Addition of oat bran reduces HDL-C and does not potentialize effect of a low-calorie diet on remission of metabolic syndrome: A pragmatic, randomized, controlled, open-label nutritional trial.
Leão, LSCS, Aquino, LA, Dias, JF, Koifman, RJ
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:126-130
Abstract
OBJECTIVES It is unclear whether addition of soluble fiber to a low-calorie diet potentializes weight loss and amelioration of metabolic syndrome (MetS). The aim of this study was to analyze the effects of oat bran on prevalence of MetS and associated disorders. METHODS A pragmatic, randomized controlled, 6-wk nutritional trial was carried out with 154 outpatients (mean age 47.6 ± 12.6 y of age). The intervention group (n = 83) received a low-calorie diet plus 40 g/d of oat bran; the control group (n = 71) received a low-calorie diet only. MetS parameters and prevalence were calculated and compared (using two-tailed statistical tests) before and after follow-up. RESULTS After follow-up, a significant but similar reduction was observed in MetS prevalence (40% reduction, 63% and 64.8% prevalence in intervention and control groups, respectively; P = 0.226), body mass index, body weight, waist circumference, systolic and diastolic blood pressures, triacylglycerides, and blood glucose levels in both groups (P < 0.05). Mean high-density lipoprotein cholesterol (HDL-C) was reduced in the intervention group (43.6 ± 9.6 to 41.2 ± 9.5 mg/dL; P = 0.025), but not in the control group (44.6 ± 10.5 to 44.5 ± 12.1 mg/dL; P = 0.890). There was no significant difference in any of the variables between the groups, although the P-value for HDL-C was almost significant (P = 0.078). Calorie and dietetic fiber intake during the 6-wk period were similar in both groups. CONCLUSIONS Daily consumption of oat bran did not potentialize the beneficial effects of a traditional low-calorie diet on the prevalence of MetS and associated disorders. Additionally, it reduced HDL-C.
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The role of free triiodothyronine in high-density lipoprotein cholesterol metabolism.
Huang, F, Wu, L, Qiu, Y, Bu, K, Huang, H, Li, B
Medicine. 2019;(36):e17016
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Abstract
The aim of this study was to analyze the correlation between free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and serum high-density lipoprotein cholesterol (HDL-C), and to explore the significance of FT3 in HDL-C metabolism in people with normal thyroid function.A total of 461 Chinese, aged ≥28 years, from a college community in Nanning, Guangxi, were enrolled for a cross-sectional epidemiological investigation of metabolic syndrome from October 2016 to November 2016. Height, weight, blood pressure, total cholesterol, HDL-C, triglyceride (TG), fasting glucose (FPG), FT3, FT4, and TSH were measured for each individual. Multiple linear regression analysis was used to evaluate the correlation between FT3, FT4, TSH, and HDL-C.After controlling for sex, age, body mass index (BMI), smoking, drinking, and other confounding factors, FT3 was negatively correlated with HDL-C levels, on average, when FT3 increased by 1 pmol/L, HDL-C decreased by 0.143 mmol /L with a statistically significant difference (P < .001). FT4 was positively correlated with HDL-C, and HDL-C increased by 0.016 mmol/L for every 1-pmol/L increase in FT4. TSH was negatively correlated with HDL-C, and HDL-C decreases by 0.010 mmol/L for every 1-μIU/mL increase in TSH, but the differences were not statistically significant (P > .05).FT3 may be an important factor affecting HDL-C levels. The detection and regulation of thyroid hormone (especially FT3) in patients with low HDL-C, as well as the detection of HDL-C in patients with thyroid dysfunction, is important to prevent the occurrence of cardiovascular diseases.
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Cardiovascular outcomes during extended follow-up of the AIM-HIGH trial cohort.
Probstfield, JL, Boden, WE, Anderson, T, Branch, K, Kashyap, M, Fleg, JL, Desvigne-Nickens, P, McBride, R, McGovern, M, ,
Journal of clinical lipidology. 2018;(6):1413-1419
Abstract
BACKGROUND Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) and elevated triglycerides are independent predictors of cardiovascular (CV) events, though randomized trials of HDL-C-raising therapies to reduce clinical events have been largely disappointing. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial failed to show that extended release niacin (ERN) reduced CV events in patients with atherogenic dyslipidemia who were on statin-based therapy. OBJECTIVE We sought to determine whether extended follow-up of AIM-HIGH participants changed these null results. METHODS AIM-HIGH was a placebo-controlled trial of 3414 patients with established CV disease, low baseline HDL-C, and elevated triglycerides levels randomized to ERN 1500-2000 mg/d vs placebo. Participants also received simvastatin with or without ezetimibe to attain on-treatment low-density lipoprotein cholesterol levels of 40-80 mg/dL. The trial was halted after a mean 3-year follow-up because of futility. RESULTS Among 3236 participants alive at the end of blinded study, 2613 (81%; ERN = 1,312, placebo = 1301) were followed a mean 1.1 additional years. Ninety-five percent of subjects remained on statin, but only 4% on ERN. At a mean total follow-up of 4.1 years, there were 343 primary CV endpoints in the ERN arm and 305 CV endpoints in placebo participants (HR 1.11, 95% CI 0.96, 1.30). Ischemic stroke was also not significantly different after extended follow-up in the two groups (2.2% vs 1.5%, P = .13). CONCLUSIONS In patients with CV disease and atherogenic dyslipidemia on statin-based therapy, 3 years of ERN treatment did not lower CV event rates. An additional year of follow-up off assigned treatment did not alter these findings.
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ACE, APOA5, and MTP Gene Polymorphisms Analysis in Relation to Triglyceride and Insulin Levels in Pediatric Patients.
Carranza-González, L, León-Cachón, RBR, González-Zavala, MA, Ríos-Ibarra, C, Morlett-Chávez, J, Sánchez-Domínguez, C, Cepeda-Nieto, A, Salinas-Santander, M
Archives of medical research. 2018;(2):94-100
Abstract
BACKGROUND AND AIMS Obesity is a complex, chronic, and multifactorial disease that has become a major, and worldwide, public health problem contributing to an increased number of pathologies, including type 2 diabetes, cardiovascular disease, hyperlipidemia, and metabolic syndrome, thus suggesting a commolon origin. A diet high in sugar and fats coupled with a sedentary lifestyle has a major role in the development of obesity. However, the genetic background has also been associated with body fat accumulation. The aim of this study was to assess the effect ofACE-rs4646994, APOA5-rs662799, and MTP-rs1800591 gene polymorphisms on clinical and biochemical parameters and to evaluate the association with body phenotypes in children and adolescent population of Saltillo, Coahuila, Mexico. METHODS Anthropometric, clinical, biochemical parameters and BMI were obtained from 405 children and adolescents. The BMI was used to determine the body phenotype. The rs4646994 gene polymorphism was determined by PCR, whereas rs662799 and rs1800591 were determined by PCR-RFLP. The obtained results were analyzed to determine their association of these single nucleotide polymorphisms with body phenotype and biochemical parameters. RESULTS TT genotype for APOA5-rs662799 was associated with increased levels of HDL-C in the analyzed population (p <0.05). The ACErs4646994gene polymorphism is associated with high Insulin levels, HOMAIR index, and triglyceride levels, mainly when presenting a I/I genotype (p <0.05). CONCLUSION The polymorphic allele of the ACE gene is capable of modulating triglyceride levels, insulin levels and HOMA-IR index in the evaluated population; it must be highlighted that this has not been reported in other studied populations elsewhere.
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Triglycerides/High density lipoprotein cholesterol ratio as a cardiometabolic risk marker in children and adolescents from Mérida city, Venezuela.
Aguirre, M, Briceño, Y, Gómez-Pérez, R, Zerpa, Y, Camacho, N, Paoli, M
Endocrinologia, diabetes y nutricion. 2018;(2):74-83
Abstract
OBJECTIVE To determine the behavior of the triglycerides/HDL-cholesterol ratio (TG/HDL) as a cardiometabolic risk marker in children and adolescents from Mérida, Venezuela. METHODS A total of 1292 children and adolescents aged 7-18 years who attended educational institutions in the Libertador Municipality were enrolled into this study. Anthropometric measurements and blood pressure values were recorded. Fasting blood glucose, insulin and lipid levels were measured. The TG/HDL ratio, HOMA-IR, and QUICKI indexes were calculated. Subjects were categorized as with and without cardiometabolic risk based on the presence or absence of 2or more risk factors. Cut-off points for the TG/HDL ratio were determined by constructing ROC curves. RESULTS Significantly higher mean TG/HDL ratios were found in pubertal (2.2 ± 1.7) as compared to prepubertal subjects (1.8 ± 1.5; P=.001), with no sex differences. Two or more risk factors were found in 14.7% (n=192) of the participants, in whom TG/HDL ratios were significantly higher as compared to those with no risk (3.5±2.9 versus 1.6±0.8 in prepubertal and 4.1 ± 3.5 versus 1.8 ± 0.9 in pubertal subjects; P=.0001). According to cardiometabolic risk, cut-off points for the TG/HDL ratio of 1.8 and 2.5 were found for prepubertal and pubertal children respectively. These cut-off points showed risks (odds ratio) higher than 2.5 for conditions such as metabolic syndrome, elevated non-HDL-C, abdominal obesity, and elevated HOMA-IR. CONCLUSION In this sample of children and adolescents, an elevated TG/HDLc ratio was found to be a good marker for predicting cardiometabolic risk.
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High-density lipoprotein-cholesterol functionality and metabolic syndrome: Protocol for review and meta-analysis.
Roever, L, Resende, ES, Diniz, ALD, Penha-Silva, N, O'Connell, JL, Gomes, PFS, Zanetti, HR, Roerver-Borges, AS, Veloso, FC, Souza, FR, et al
Medicine. 2018;(24):e11094
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INTRODUCTION The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia and an increased risk of cardiovascular events. One function of high-density lipoprotein (HDL) cholesterol (HDL-C) is the cholesterol-efflux pathway, which is the pathway where cholesterol is removed from macrophages within the arterial walls back into the bloodstream and out to the liver. As one of the key functions of HDL, their hypothesis was that if they could measure HDL-C-efflux capacity, they would have a better handle on the role of HDL in atherosclerosis. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between HDL-C functionality and MetS. The aim of this study is to examine this association of HDL-C functionality with MetS in different ages and sex. METHODS AND ANALYSIS The update systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (i.e., PubMed, EMBASE, Web of Science, and Google Scholar). Studies that examined the association between HDL-C functionality and MetS; focused on cohort, case-control, and cross-sectional studies; were conducted among in adults aged 40 to 70 years; provided sufficient data for calculating odds ratio or relative risk with a 95% confidence interval; were published as original articles written in English or other languages; and have been published until January 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators. ETHICS AND DISSEMINATION Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER PROSPERO (CRD42018083465).