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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% : 1.13,1.80, -value=0.003), even after adjustment for confounding factors (adj.OR=1.36, 95% : 1.06,1.74, -value=0.016) and (BMI-adj.OR=1.29, 95% : 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 -
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.
PubMed: 38879446
DOI: 10.1161/JAHA.123.034434 -
Frontiers in Public Health 2023The global prevalence of Non-alcoholic fatty liver disease (NAFLD) is about 25% worldwide making it an actual health disaster. This study aimed to assess non-alcoholic...
INTRODUCTION
The global prevalence of Non-alcoholic fatty liver disease (NAFLD) is about 25% worldwide making it an actual health disaster. This study aimed to assess non-alcoholic fatty liver disease (NAFLD)-related knowledge in a sample of Egyptians.
MATERIALS AND METHODS
This exploratory cross-sectional study was conducted on 3,124 individuals using 2000 online and 1,124 printed questionnaire forms. These questionnaires, covering sociodemographic characteristics and fatty liver-related knowledge, comprised 30 items. These items include ten questions on definition, symptoms, and complications: 14 about risk factors, and six about prevention and therapy. The data were analyzed using SPSS. Categorical variables were expressed in proportions and percentages. Chi-square and Fisher's exact tests were applied as appropriate. For quantitative variables, the t-test, Mann-Whitney U test, Kruskal-Wallis test, and ANOVA test were used for comparisons.
RESULTS
A total of 3,124 respondents were enrolled in the current study. More than half (57%) were females, and 25% ranged in age from 18 to 29. 10.8% of the participants believed that fatty liver patients were asymptomatic, and 34% knew that fatty liver disease was caused by fat accumulation. Regarding predisposing factors, hypercholesterolemia, increased fat in the diet, and obesity had the highest proportion of accurate responses (60, 54, and 46.6%, respectively). On the other hand, 89.3% believed it could be prevented, and 81.4% of the respondents knew that weight reduction could prevent the condition. All respondents (100%) stated wrongly that it was a familial disease related to aging, and most participants (97.3%) did not believe that fatty liver could be treated. Females demonstrated a significantly higher score in preventive measures, while the employed participants scored significantly higher in general knowledge of fatty liver, risk factors, and preventive measures.
CONCLUSION
Despite the increasing NAFLD prevalence, the current study indicated that Egyptians had fair to moderate knowledge about fatty liver and its risk factors, preventive measures, and therapy. However, a false belief was documented by all respondents that it is a disease that runs in families and occurs only in old age. A fundamental shift in healthcare management with a prioritization of prevention, proactive measures, and early detection of NAFLD should be emphasized.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Cross-Sectional Studies; Female; Male; Adult; Egypt; Surveys and Questionnaires; Health Knowledge, Attitudes, Practice; Risk Factors; Middle Aged; Adolescent; Young Adult; Prevalence; North African People
PubMed: 38872989
DOI: 10.3389/fpubh.2023.1290842 -
Revue Medicale de Liege Jun 2024Prevention of cardiovascular disease remains a key-objective from a health care point of view. The present article focuses on primary prevention, i.e. to prevent a first... (Review)
Review
Prevention of cardiovascular disease remains a key-objective from a health care point of view. The present article focuses on primary prevention, i.e. to prevent a first cardiovascular event among at-risk people. The first step is to evaluate the cardiovascular risk level (low to moderate, high, very high), which allows to fix target goals. It is especially the case regarding the management of dyslipidaemias. Lipid abnormalities are considered as a major coronary risk factor (especially, LDL or even better non-HDL cholesterol according to recent guidelines). Theoretically, it is quite easy to control this risk factor thanks to available lipid-lowering drugs, yet this goal remains insufficiently reached in clinical practice. The second step is to prescribe, in addition to life-style measures, the best pharmacological treatment. In most cases, it is a statin that should be well titrated, eventually combined with ezetimibe and/or bempedoic acid, to reach the set objectives. Finally, it is important to convince the at-risk individual by providing the valuable information regarding the benefits/risks ratio of the therapy and to verify a good drug compliance in the long run. Indeed, as dyslipidaemia is asymptomatic, people in primary prevention too easily tend to neglect (and eventually stop) the valuable therapy, also because statins have been widely (yet unfairly) criticized by some people in recent years.
Topics: Humans; Dyslipidemias; Cardiovascular Diseases; Primary Prevention; Hypolipidemic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38869128
DOI: No ID Found -
Journal of the Turkish German... Jun 2024Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal...
Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal at an early age due to bilateral oophorectomy or repeated ovarian surgery. In addition, some medical therapies used for endometriosis, such as gonadotropin releasing hormone agonists or progestins reduce bone mineral density. Furthermore, women with endometriosis have a higher background risk of cardiovascular disorders and hypercholesterolemia. Hence, it is important to recommend the use of hormone replacement therapy (HRT) to these women when they become menopausal, at least until the age of natural menopause. Although based on limited data, there is a possibility of reactivation of symptoms of endometriosis or its lesions, and a theoretical possibility of malignant transformation, although this remains unproven. Therefore, women should be advised in the light of this information before starting HRT after the age of natural menopause and are asked to seek help if they experience symptoms that may indicate these changes. Estrogen only HRT should be avoided and combined HRT preparations should be recommended, even after a hysterectomy.
PubMed: 38869053
DOI: 10.4274/jtgga.galenos.2024.2023-11-4 -
European Heart Journal Supplements :... Apr 2024There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering...
There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering drugs is not clear. According to animal studies with recombinant lipoprotein A-1, the composition of atherosclerosis changes within 40 h (with variations in lipid and inflammatory contents). Progression-regression studies of atherosclerosis in humans confirm the data, highlighting a rapid change in the plaque over 5 weeks. The data are also in line with what emerges from the survival curves of the old study comparing atorvastatin 80 mg vs. placebo (Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering). The spacing of the curves occurs after only 4 weeks, indicating the precociousness of the favourable effects of powerful statins. Finally, a recent Odyssey analysis compared the risk of cardiac death and coronary revascularization between a group in which alirocumab lowered LDL cholesterol to below 15 mg (Group 1 and in which the drug was therefore stopped) against the subjects in the placebo group (Group 2), applying a propensity score matching. The primary endpoint occurred in a lower percentage of patients in Group 1 (6.4 vs. 8.4%). Furthermore, patients in Group 1 had a significantly lower hazard ratio (HR) for major adverse cardiovascular events [0.72; 95% confidence interval (CI) 0.51-0.997; = 0.047] compared with the entire alirocumab group vs. placebo (HR 0.85; 95% CI 0.78-0.93; < 0.001). According to these preliminary observations, aggressive and early treatment of hypercholesterolaemia in subjects with acute coronary syndrome translates into improved clinical results compared with a strategy that provides for more gradual control. These data will need to be confirmed through further prospective clinical studies and ideally with early conducted atherosclerosis regression studies.
PubMed: 38867873
DOI: 10.1093/eurheartjsupp/suae010 -
Lipids in Health and Disease Jun 2024Familial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age....
BACKGROUND
Familial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age. Approximately 95% of FH-causing genetic variants that have been identified are in the LDLR gene. However, only 10% of the FH population worldwide has been diagnosed and adequately treated, due to the existence of numerous unidentified variants, uncertainties in the pathogenicity scoring of many variants, and a substantial number of individuals lacking access to genetic testing.
OBJECTIVE
The aim of this study was to identify a novel variant in the LDLR gene that causes FH in a Chinese family, thereby expanding the spectrum of FH-causing variants.
METHODS
Patients were recruited from Beijing Anzhen Hospital, Capital Medical University. FH diagnosis was made according to the Dutch Lipid Clinical Network (DLCN) criteria. Whole-exome sequencing (WES) was conducted to identify the FH-causing variant in the proband, and amplicon sequencing was used to verify the variant in his family members.
RESULTS
A three-generation Chinese family was recruited, and two FH patients were clinically diagnosed, both without known FH-causing variants. These two FH patients and another possible patient carried a novel variant, NC_000019.9(NM_000527.5):c.89_92dup (NP_000518.1:p.Phe32Argfs*21), in the ligand-binding domain of the low-density lipoprotein (LDL) receptor that led to a frameshift. The FH adults in the family showed severe clinical symptoms and statin therapy resistance.
CONCLUSION
This study identified a novel pathogenic LDLR variant, c.89_92dup, associated with severe FH clinical manifestations and statin therapy resistance.
Topics: Humans; Hyperlipoproteinemia Type II; Receptors, LDL; Male; Frameshift Mutation; Female; Pedigree; Adult; Middle Aged; Exome Sequencing
PubMed: 38867270
DOI: 10.1186/s12944-024-02173-2 -
Journal of Lipid Research Jun 2024Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy...
Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis and fecal neutral steroid excretion. CONCLUSIONS: MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.
PubMed: 38866328
DOI: 10.1016/j.jlr.2024.100576 -
Life Sciences Jun 2024Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major... (Review)
Review
Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major contributing factor to their onset. Epidemiological and clinical studies have linked high levels of low-density lipoprotein (LDL) emanating from distorted cholesterol homeostasis as its major predisposing factor. Cholesterol homeostasis, which involves maintaining the balance in body cholesterol level, is mediated by several proteins or receptors, transcription factors, and even genes, regulating cholesterol influx (through dietary intake or de novo synthesis) and efflux (by their conversion to bile acids). Previous knowledge about CVDs management has evolved around modulating these receptors' activities through synthetic small molecules/antibodies, with limited interest in natural products. The central roles of the cholesteryl ester transfer protein (CETP), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cytochrome P450 family 7 subfamily A member 1 (CYP7A1), among other proteins or receptors, have fostered growing scientific interests in understanding more on their regulatory activities and potential as drug targets. We present up-to-date knowledge on the contributions of CETP, PCSK9, and CYP7A1 toward CVDs, highlighting the clinical successes and failures of small molecules/antibodies to modulate their activities. In recommendation for a new direction to improve cardiovascular health, we have presented recent findings on natural products (including functional food, plant extracts, phytochemicals, bioactive peptides, and therapeutic carbohydrates) that also modulate the activities of CETP, PCSK-9, and CYP7A1, and emphasized the need for more research efforts redirected toward unraveling more on natural products potentials even at clinical trial level for CVD management.
PubMed: 38866219
DOI: 10.1016/j.lfs.2024.122823