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Paediatric and Perinatal Epidemiology Jun 2024Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring.
BACKGROUND
Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring.
OBJECTIVES
We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health.
METHODS
The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma.
RESULTS
Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias.
CONCLUSIONS
We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.
PubMed: 38886184
DOI: 10.1111/ppe.13097 -
Epigenomics Jun 2024Methylation of , and CpG sites was assessed in patients with familial hypercholesterolemia (FH). DNA methylation of was analyzed by pyrosequencing in 131 FH patients...
Methylation of , and CpG sites was assessed in patients with familial hypercholesterolemia (FH). DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects. , and methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. and methylation was higher in MD and non-MD groups than NL subjects ( < 0.05). , and methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients ( < 0.05). Differential methylation of , and is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.
PubMed: 38884343
DOI: 10.1080/17501911.2024.2351792 -
MedRxiv : the Preprint Server For... Jun 2024This study explored the association between dyslipidemia and sleep and nighttime behavior disorders (SNBD) in the elderly.
High serum Cholesterol and Triglyceride levels in older adults: associations with sleep and nighttime behavior disorders at baseline and a prediction analysis of incidental cases at 12 months follow-up.
INTRODUCTION
This study explored the association between dyslipidemia and sleep and nighttime behavior disorders (SNBD) in the elderly.
METHODS
ADNI population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between dyslipidemia and SNBD at baseline and 12 months. Relevant confounders were adjusted for.
RESULTS
Among the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 (IQR: 68, 78). At baseline, 357 (16%) had SNBD, and 327 (18%) at 12 months; 187 were incident cases.There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%, -value=0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%, -value=0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL, -value<0.001).Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR=1.43, 95%CI: 1.13,1.80, -value=0.003), even after adjustment for confounding factors (adj.OR=1.36, 95%CI: 1.06,1.74, -value=0.016) and (BMI-adj.OR=1.29, 95%CI: 1.00,1.66, -value=0.048). None of the dyslipidemia forms did predict incident cases at 12 months.
CONCLUSIONS
Hypertriglyceridemia, but not hypercholesterolemia, was associated with higher odds of SNBD. None of the dyslipidemia forms predicted incidental SNBD over 12 months.
PubMed: 38883726
DOI: 10.1101/2024.06.05.24308529 -
American Heart Journal Plus :... Jul 2024Standard Modifiable Cardiovascular Risk Factors (SMuRF) such as hypertension, diabetes mellitus, hypercholesterolemia, and smoking have long been established in the...
Prevalence, predictors, and in-hospital outcomes of ST-elevation myocardial infarction among young adults without traditional cardiovascular risk factors in the United States.
BACKGROUND
Standard Modifiable Cardiovascular Risk Factors (SMuRF) such as hypertension, diabetes mellitus, hypercholesterolemia, and smoking have long been established in the etiology of atherosclerotic disease. Studies suggest that patients without any of these risk factors (SMuRF-less) who present with ST-elevation myocardial infarction have worse outcomes.
METHODS
The National Inpatient Sample databases (2016 to 2020) was queried to identify STEMI admissions as a principal diagnosis using ICD 10 codes. The study population aged 18 to 45 years were divided into cohorts of SMuRF and SMuRF-less based on the presence of ≥1 risk factor (hypertension, diabetes mellitus, hyperlipidemia, and smoking), and in-hospital outcomes were compared.
RESULTS
41,990 patients were identified as the final study population. 38,495 patients were identified as SMuRF, and 3495 patients were SMuRF-less. Compared to SMuRF patients, SMuRF-less patients are more likely to be females (23.2 % vs. 21.2 %), have congestive heart failure (16.6 % vs. 13.7 %, < 0.01) but less likely to have obesity (13.7 % vs 28.0 %, < 0.01) In evaluating outcomes, SMuRF-less patients had higher adjusted in-hospital mortality (aOR 2.6, CI 1.5-4.2, < 0.01), Cardiogenic shock (aOR 1.8, CI 1.3-2.5, p < 0.01), acute kidney injury (aOR 1.4, CI 1.0-1.9, = 0.02), and Extramembrane Corporeal Oxygenation (aOR 4.1, CI 1.1-15.1, = 0.03). Fluid and electrolyte abnormalities was an independent predictor of mortality among SMuRF-less patients (aOR 3.82, CI 1.3-11.2, < 0.01).
CONCLUSION
Young patients who present with STEMI and have no traditional cardiovascular risk factors have worse in-hospital outcomes. Further research is needed to evaluate the impact of non-traditional risk factors on acute myocardial infarction.
PubMed: 38882592
DOI: 10.1016/j.ahjo.2024.100408 -
Heliyon Jun 2024Hypercholesterolemia is a metabolic disease characterized by elevated cholesterol level in the blood, which is a risk factor for many diseases. Probiotic intervention...
Limosilactobacillus fermentum TY-S11 ameliorates hypercholesterolemia via promoting cholesterol excretion and regulating gut microbiota in high-cholesterol diet-fed apolipoprotein E-deficient mice.
Hypercholesterolemia is a metabolic disease characterized by elevated cholesterol level in the blood, which is a risk factor for many diseases. Probiotic intervention may be one of the ways to improve hypercholesterolemia. In this study, three strains with better cholesterol removal ability were selected from 60 strains of lactic acid bacteria, and were orally administered to apolipoprotein E-deficient mice on a high-cholesterol diet. Among the three strains, only TY-S11, which was isolated from the intestine of a longevity person, significantly improved serum and liver lipid levels in hypercholesterolemic mice. Further study found that TY-S11 promoted the excretion of cholesterol in the feces and inhibited the absorption of cholesterol in the small intestine. As for gut microbiota, the results showed that TY-S11 not only prevented the reduction of diversity caused by high-cholesterol diet, but also increased the contents of short-chain fatty acids in feces. These results confirmed the ameliorative effect of TY-S11 on hypercholesterolemia.
PubMed: 38882320
DOI: 10.1016/j.heliyon.2024.e32059 -
Atherosclerosis Jun 2024Dysregulated cholesterol metabolism is a hallmark of atherosclerotic cardiovascular diseases, yet our understanding of how endogenous cholesterol synthesis affects...
BACKGROUND AND AIMS
Dysregulated cholesterol metabolism is a hallmark of atherosclerotic cardiovascular diseases, yet our understanding of how endogenous cholesterol synthesis affects atherosclerosis is not clear. The energy sensor AMP-activated protein kinase (AMPK) phosphorylates and inhibits the rate-limiting enzyme in the mevalonate pathway HMG-CoA reductase (HMGCR). Recent work demonstrated that when AMPK-HMGCR signaling was compromised in an Apoe model of hypercholesterolemia, atherosclerosis was exacerbated due to elevated hematopoietic stem and progenitor cell mobilization and myelopoiesis. We sought to validate the significance of the AMPK-HMGCR signaling axis in atherosclerosis using a non-germline hypercholesterolemia model with functional ApoE.
METHODS
Male and female HMGCR S871A knock-in (KI) mice and wild-type (WT) littermate controls were made atherosclerotic by intravenous injection of a gain-of-function Pcsk9-adeno-associated virus followed by high-fat and high-cholesterol atherogenic western diet feeding for 16 weeks.
RESULTS
AMPK activation suppressed endogenous cholesterol synthesis in primary bone marrow-derived macrophages from WT but not HMGCR KI mice, without changing other parameters of cholesterol regulation. Atherosclerotic plaque area was unchanged between WT and HMGCR KI mice, independent of sex. Correspondingly, there were no phenotypic differences observed in hematopoietic progenitors or differentiated immune cells in the bone marrow, blood, or spleen, and no significant changes in systemic markers of inflammation. When lethally irradiated female mice were transplanted with KI bone marrow, there was similar plaque content relative to WT.
CONCLUSIONS
Given previous work, our study demonstrates the importance of preclinical atherosclerosis model comparison and brings into question the importance of AMPK-mediated control of cholesterol synthesis in atherosclerosis.
PubMed: 38880706
DOI: 10.1016/j.atherosclerosis.2024.117608 -
Cardiovascular Diabetology Jun 2024There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG).
METHODS
In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications.
RESULTS
Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques.
CONCLUSION
In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient.
TRIAL REGISTRATION
Clinicaltrials.gov number, NCT03975478).
Topics: Humans; Male; Female; Gastric Bypass; Gastrectomy; Adult; Middle Aged; Cholesterol, LDL; Treatment Outcome; Obesity, Morbid; Time Factors; Biomarkers; Weight Loss; Remission Induction; Laparoscopy; Hypercholesterolemia; Sitosterols
PubMed: 38879559
DOI: 10.1186/s12933-024-02296-x -
Journal of the American Heart... Jun 2024Familial hypercholesterolemia (FH), while highly prevalent, is a significantly underdiagnosed monogenic disorder. Improved detection could reduce the large number of...
BACKGROUND
Familial hypercholesterolemia (FH), while highly prevalent, is a significantly underdiagnosed monogenic disorder. Improved detection could reduce the large number of cardiovascular events attributable to poor case finding. We aimed to assess whether machine learning algorithms outperform clinical diagnostic criteria (signs, history, and biomarkers) and the recommended screening criteria in the United Kingdom in identifying individuals with FH-causing variants, presenting a scalable screening criteria for general populations.
METHODS AND RESULTS
Analysis included UK Biobank participants with whole exome sequencing, classifying them as having FH when (likely) pathogenic variants were detected in their , , or genes. Data were stratified into 3 data sets for (1) feature importance analysis; (2) deriving state-of-the-art statistical and machine learning models; (3) evaluating models' predictive performance against clinical diagnostic and screening criteria: Dutch Lipid Clinic Network, Simon Broome, Make Early Diagnosis to Prevent Early Death, and Familial Case Ascertainment Tool. One thousand and three of 454 710 participants were classified as having FH. A Stacking Ensemble model yielded the best predictive performance (sensitivity, 74.93%; precision, 0.61%; accuracy, 72.80%, area under the receiver operating characteristic curve, 79.12%) and outperformed clinical diagnostic criteria and the recommended screening criteria in identifying FH variant carriers within the validation data set (figures for Familial Case Ascertainment Tool, the best baseline model, were 69.55%, 0.44%, 65.43%, and 71.12%, respectively). Our model decreased the number needed to screen compared with the Familial Case Ascertainment Tool (164 versus 227).
CONCLUSIONS
Our machine learning-derived model provides a higher pretest probability of identifying individuals with a molecular diagnosis of FH compared with current approaches. This provides a promising, cost-effective scalable tool for implementation into electronic health records to prioritize potential FH cases for genetic confirmation.
Topics: Humans; Hyperlipoproteinemia Type II; Machine Learning; Female; Male; Proprotein Convertase 9; Apolipoprotein B-100; Middle Aged; Receptors, LDL; United Kingdom; Exome Sequencing; Genetic Testing; Adult; Predictive Value of Tests; Genetic Predisposition to Disease; Mutation
PubMed: 38879446
DOI: 10.1161/JAHA.123.034434 -
Journal of Neurology Jun 2024This study was an introduction to the Swedish ALSrisc Study and explored the association of lifestyle and medical conditions, with risk and progression of amyotrophic...
BACKGROUND
This study was an introduction to the Swedish ALSrisc Study and explored the association of lifestyle and medical conditions, with risk and progression of amyotrophic lateral sclerosis (ALS).
METHODS
We included 265 newly diagnosed ALS patients during 2016-2022 in Stockholm and 207 ALS-free siblings and partners of the patients as controls. Information on body mass index (BMI), smoking, and history of head injuries, diabetes mellitus, hypercholesterolemia, and hypertension was obtained through the Euro-MOTOR questionnaire at recruitment. Patients were followed from diagnosis until death, invasive ventilation, or November 30, 2022.
RESULTS
Higher BMI at recruitment was associated with lower risk for ALS (OR 0.89, 95%CI 0.83-0.95), especially among those diagnosed after 65 years. One unit increase in the average BMI during the 3 decades before diagnosis was associated with a lower risk for ALS (OR 0.94, 95%CI 0.89-0.99). Diabetes was associated with lower risk of ALS (OR 0.38, 95%CI 0.16-0.90), while hypercholesterolemia was associated with higher risk of ALS (OR 2.10, 95%CI 1.13-3.90). Higher BMI at diagnosis was associated with lower risk of death (HR 0.91, 95%CI 0.84-0.98), while the highest level of smoking exposure (in pack-years) (HR 1.90, 95%CI 1.20-3.00), hypercholesterolemia (HR 1.84, 95%CI 1.06-3.19), and hypertension (HR 1.76, 95%CI 1.03-3.01) were associated with higher risk of death, following ALS diagnosis.
CONCLUSIONS
Higher BMI and diabetes were associated with lower risk of ALS. Higher BMI was associated with lower risk of death, whereas smoking (especially in high pack-years), hypercholesterolemia, and hypertension were associated with higher risk of death after ALS diagnosis.
PubMed: 38878106
DOI: 10.1007/s00415-024-12496-w -
Transplantation Proceedings Jun 2024The use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab, to treat drug-resistant hypercholesterolemia is increasing; however, to...
The use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab, to treat drug-resistant hypercholesterolemia is increasing; however, to date there have been no studies on the use of alirocumab to treat the hyperlipidemia that follows liver transplantation. Here we report a case of successful management of hyperlipidemia, albeit without total reversal of elevated serum triglycerides, with alirocumab monotherapy in a liver transplantation patient who was resistant to rosuvastatin and fenofibrate. In terms of safety, only transient palpitations following the first few alirocumab injections were recorded. This case illustrates that alirocumab can be a viable option for patients who experience poor lipid control after liver transplantation.
PubMed: 38876927
DOI: 10.1016/j.transproceed.2024.05.015