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1.
Lipids Health Dis ; 23(1): 320, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39342373

ABSTRACT

INTRODUCTION: Sleep disorders, particularly insomnia and obstructive sleep apnea, are associated with dyslipidemia in the general population. The study's aim was to explore the association between pathological Cholesterol and Triglyceride levels, and sleep and nighttime behavior disorders (SNBD) in older adults, whether they might predict SNBD onset, and to emphasize the role of body mass index (BMI) in this association. METHODS: Alzheimer's Disease Neuroimaging Initiative (ADNI) population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between hypercholesterolemia, hypertriglyceridemia, and SNBD at baseline and at 12 months. Relevant confounders, particularly BMI, were adjusted for. RESULTS: Among the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 years (IQR: 68, 78). At baseline, 357 (16%) had SNBD and 327 (18%) at 12 months; 187 of them were incident cases. There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%, P-value = 0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%, P-value = 0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL, P-value < 0.001). Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR = 1.43, 95%CI: 1.13,1.80, P-value = 0.003), even after adjustment for confounding factors (adj. OR = 1.36, 95%CI: 1.06,1.74, P-value = 0.016) and (BMI-adj. OR = 1.29, 95%CI: 1.00,1.66, P-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. The association was independent of BMI. None of the dyslipidemia forms did predict incident SNBD over 12 months. Sleep disorders should motivate a systematic screening of dyslipidemia in older adults and vice versa.


Subject(s)
Body Mass Index , Hypercholesterolemia , Hypertriglyceridemia , Humans , Aged , Female , Hypertriglyceridemia/epidemiology , Hypertriglyceridemia/complications , Hypertriglyceridemia/blood , Male , Hypercholesterolemia/epidemiology , Hypercholesterolemia/complications , Triglycerides/blood , Follow-Up Studies , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/complications , Sleep Wake Disorders/blood , Alzheimer Disease/epidemiology , Alzheimer Disease/blood , Sleep/physiology
2.
Korean J Intern Med ; 39(5): 717-730, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39252486

ABSTRACT

Elevated blood cholesterol and triglyceride levels induced by secondary causes are frequently observed. The identification and appropriate handling of these causes are essential for secondary dyslipidemia treatment. Major secondary causes of hypercholesterolemia and hypertriglyceridemia include an unhealthy diet, diseases and metabolic conditions affecting lipid levels, and therapeutic side effects. It is imperative to correct secondary causes prior to initiating conventional lipid-lowering therapy. Guideline-based lipid therapy can then be administered based on the subsequent lipid levels.


Subject(s)
Consensus , Dyslipidemias , Hypolipidemic Agents , Humans , Hypolipidemic Agents/therapeutic use , Dyslipidemias/blood , Dyslipidemias/diagnosis , Dyslipidemias/drug therapy , Dyslipidemias/therapy , Biomarkers/blood , Hypertriglyceridemia/diagnosis , Hypertriglyceridemia/blood , Hypertriglyceridemia/therapy , Risk Factors , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Hypercholesterolemia/diagnosis , Hypercholesterolemia/drug therapy , Treatment Outcome , Triglycerides/blood
3.
G Ital Cardiol (Rome) ; 25(9): 650-659, 2024 Sep.
Article in Italian | MEDLINE | ID: mdl-39239816

ABSTRACT

Due to the growing evidence of clinical benefits conferred by the reduction of low-density lipoprotein cholesterol (LDL-C) levels, the availability of multiple effective lipid-lowering agents, and guideline recommendations, clinicians not infrequently have to manage patients with low or very low LDL-C levels. In clinical practice it is essential to consider that, when LDL-C plasma concentrations are low, the Friedewald formula commonly used for LDL-C level calculation is less accurate, hence risk assessment should be integrated by using different methods for LDL-C level quantification and other parameters, such as non-high-density lipoprotein cholesterol and, where possible, apolipoprotein B, should be measured. As regards the clinical impact of low LDL-C levels, genetically determined hypocholesterolemia forms provide reassuring data on the effects of this condition in the long term, except for the forms with extremely low or undetectable LDL-C levels. Evidence from clinical studies that used highly effective lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitors, goes in the same direction. In these studies, the incidence of non-cardiovascular adverse events in patients who reached very low LDL-C levels was similar to that in the placebo arm. Overall, the fear of adverse effects should not deter intensive lipid-lowering treatment when indicated to reduce the risk of cardiovascular events.


Subject(s)
Anticholesteremic Agents , Cholesterol, LDL , Hypercholesterolemia , Humans , Anticholesteremic Agents/therapeutic use , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cholesterol, LDL/blood , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , PCSK9 Inhibitors/therapeutic use , Risk Assessment
4.
Drugs Aging ; 41(9): 699-712, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39126433

ABSTRACT

As the population ages, the demographic of adults aged 75 years and older in the U.S. is projected to grow to 45 million by 2050. Hypercholesterolemia is directly linked to atherosclerotic cardiovascular disease (ASCVD), which remains the leading cause of death in older adults. However, primary prevention of ASCVD through lipid-lowering agents remains unclear among older adults owing to limited involvement of older adults in current trials, lack of dedicated trials, and evidence primarily derived from secondary and retrospective analyses. Therefore, this article aims to (1) review key updates from the latest guidelines on treatment of hypercholesterolemia in older adults, (2) highlight limitations of the current ASCVD risk scores in the geriatric population, (3) present outcomes from key studies on the use of lipid-lowering agents and associated side effects, including a brief review of novel agents such as bempedoic acid, although very few adults over age 75 were included in these trial, and (4) finally, highlight upcoming dedicated trials of statins in older adults for the primary prevention of important geriatric outcomes as well as ASCVD.


Subject(s)
Cardiovascular Diseases , Hypercholesterolemia , Primary Prevention , Humans , Hypercholesterolemia/drug therapy , Hypercholesterolemia/complications , Aged , Primary Prevention/methods , Cardiovascular Diseases/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use
5.
Arterioscler Thromb Vasc Biol ; 44(9): 2069-2087, 2024 09.
Article in English | MEDLINE | ID: mdl-39087348

ABSTRACT

BACKGROUND: Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. METHODS: We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. RESULTS: TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating ß-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. CONCLUSIONS: In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.


Subject(s)
Atherosclerosis , Disease Models, Animal , Liver , Mice, Knockout, ApoE , Receptors, LDL , Animals , Receptors, LDL/genetics , Receptors, LDL/deficiency , Atherosclerosis/prevention & control , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/etiology , Liver/metabolism , Male , Mice, Inbred C57BL , Time Factors , Fasting/blood , Mice , Hypercholesterolemia/genetics , Hypercholesterolemia/metabolism , Hypercholesterolemia/complications , Diet, Atherogenic , Weight Gain , Mice, Knockout , Aortic Diseases/prevention & control , Aortic Diseases/genetics , Aortic Diseases/pathology , Aortic Diseases/metabolism , Lipids/blood , Apolipoproteins E
6.
Lipids Health Dis ; 23(1): 222, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039599

ABSTRACT

BACKGROUND: Sitosterolemia, an autosomal recessive condition, is characterized by impaired metabolism of plant sterols. Clinical symptoms include skin xanthoma, premature atherosclerotic disease, arthritis, and unexplained hematological abnormalities. However, there is a dearth of studies on sitosterolemia-related brain damage. METHODS: This study focused on the family of two sitosterolemia patients who presented with severe hypercholesterolemia and xanthoma. Radiological examinations, biopsies, whole-exome sequencing (WES), and plant sterol tests were conducted. RESULTS: The index patient, a 66-year-old female, initially exhibited weakness in both lower limbs and later developed urinary and fecal incontinence. Neuroimaging showed that the falx of the brain had irregular fusiform thickening. Significant tissue edema was observed around the lesions in the bilateral frontal-parietal lobes. Pathological analysis of the biopsied brain lesion revealed extensive cholesterol crystal deposition and lymphocyte infiltration in the matrix. The index patient who experienced cerebral impairment and her sister both carried two compound heterozygous variants in ATP binding cassette transporter G5 (ABCG5). These included the nonsense variants NM_022436: c.751 C > T (p.Q251X) in exon 6 and NM_022436: c.1336 C > T (p.R446X) in exon 10. A notable increase in plant sterol levels was observed in the younger sister of the index patient. CONCLUSION: This study highlights a previously unreported neurological aspect of sitosterolemia. Imaging and pathology findings suggest that cholesterol crystals may be deposited in connective tissues such as the cerebral falx and pia mater through blood circulation.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 5 , Hypercholesterolemia , Intestinal Diseases , Lipid Metabolism, Inborn Errors , Phytosterols , Humans , Female , Phytosterols/adverse effects , Aged , Hypercholesterolemia/genetics , Hypercholesterolemia/pathology , Hypercholesterolemia/complications , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/pathology , Lipid Metabolism, Inborn Errors/diagnostic imaging , Intestinal Diseases/genetics , Intestinal Diseases/pathology , Intestinal Diseases/diagnostic imaging , ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , Brain/pathology , Brain/diagnostic imaging , Exome Sequencing , Xanthomatosis/pathology , Xanthomatosis/genetics , Xanthomatosis/diagnostic imaging , Pedigree , Cholesterol/blood , Male , Sitosterols , Lipoproteins
7.
Medicina (Kaunas) ; 60(7)2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39064553

ABSTRACT

Background and Objectives: Lowering low-density lipoprotein (LDL-C) levels is critical for preventing atherosclerotic cardiovascular disease, yet some patients fail to reach the LDL-C targets despite available intensive lipid-lowering therapies. This study assessed the effectiveness and safety profile of alirocumab, evolocumab, and inclisiran in lipid reduction. Materials and Methods: A cohort of 51 patients (median (Q1-Q3) age: 49.0 (39.5-57.5) years) was analyzed. Eligibility included an LDL-C level > 2.5 mmol/L while on the maximum tolerated dose of statin and ezetimibe, a diagnosis of familial hypercholesterolemia, or a very high risk of cardiovascular diseases following myocardial infarction within 12 months prior to the study. Follow-ups and lab assessments were conducted at baseline (51 patients), 3 months (51 patients), and 15 months (26 patients) after the treatment initiation. Results: Median initial LDL-C levels 4.1 (2.9-5.0) mmol/L, decreasing significantly to 1.1 (0.9-1.6) mmol/L at 3 months and 1.0 (0.7-1.8) mmol/L at 15 months (p < 0.001). Total cholesterol also reduced significantly compared to baseline at both intervals (p < 0.001). No substantial differences in LDL-C or total cholesterol levels were observed between 3- and 15-month observations (p > 0.05). No statistically significant differences were noted in cholesterol reduction among the alirocumab, evolocumab, and inclisiran groups at 3 months. The safety profile was favorable, with no reported adverse cardiovascular events or significant changes in alanine transaminase, creatinine, or creatine kinase levels. Conclusions: Alirocumab, evolocumab, and inclisiran notably decreased LDL-C and total cholesterol levels without significant adverse effects, underscoring their potential as effective treatments in patients who do not achieve lipid targets with conventional therapies.


Subject(s)
Antibodies, Monoclonal, Humanized , Anticholesteremic Agents , Cardiovascular Diseases , Cholesterol, LDL , Hypercholesterolemia , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Male , Female , Middle Aged , Hypercholesterolemia/drug therapy , Hypercholesterolemia/complications , Hypercholesterolemia/blood , Anticholesteremic Agents/therapeutic use , Adult , Cardiovascular Diseases/prevention & control , Cholesterol, LDL/blood , Antibodies, Monoclonal/therapeutic use , Treatment Outcome , Cohort Studies , RNA, Small Interfering
8.
Curr Atheroscler Rep ; 26(9): 537-548, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38965183

ABSTRACT

PURPOSE OF THE REVIEW: This review aims to assess the variability in considering hypercholesterolemia for cardiovascular risk stratification in the general population. Recent literature on the integration of hypercholesterolemia into clinical risk scores and its interaction with other risk factors will be explored. RECENT FINDINGS: The impact of hypercholesterolemia on risk estimation varies among different cardiovascular risk calculators. Elevated lipid levels during early life stages contribute to atherosclerotic plaque development, influencing disease severity despite later treatment initiation. The interplay between low-density lipoprotein cholesterol (LDLc), inflammatory markers and non-LDL lipid parameters enhances cardiovascular risk stratification. Studies have also examined the role of coronary artery calcium (CAC) score as a negative risk marker in populations with severe hypercholesterolemia. Furthermore, polygenic risk scores (PRS) may aid in diagnosing non-monogenic hypercholesterolemia, refining cardiovascular risk stratification and guiding lipid-lowering therapy strategies. Understanding the heterogeneity in risk estimation and the role of emerging biomarkers and imaging techniques is crucial for optimizing cardiovascular risk prediction and guiding personalized treatment strategies in individuals with hypercholesterolemia.


Subject(s)
Cardiovascular Diseases , Hypercholesterolemia , Humans , Hypercholesterolemia/complications , Hypercholesterolemia/epidemiology , Hypercholesterolemia/diagnosis , Risk Assessment/methods , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Heart Disease Risk Factors , Biomarkers/blood , Cholesterol, LDL/blood , Risk Factors
9.
Med Clin (Barc) ; 163(7): 317-322, 2024 10 18.
Article in English, Spanish | MEDLINE | ID: mdl-39003112

ABSTRACT

BACKGROUND AND AIMS: The criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results. METHODS: A retrospective study of patients treated with PCSK9i at Vall d'Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed. RESULTS: A total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity. CONCLUSION: PCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials.


Subject(s)
Antibodies, Monoclonal, Humanized , Anticholesteremic Agents , Cardiovascular Diseases , Cholesterol, LDL , Hypercholesterolemia , PCSK9 Inhibitors , Humans , Male , Female , Antibodies, Monoclonal, Humanized/therapeutic use , Retrospective Studies , Middle Aged , Hypercholesterolemia/drug therapy , Hypercholesterolemia/complications , Aged , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/etiology , Cardiovascular Diseases/epidemiology , PCSK9 Inhibitors/therapeutic use , Anticholesteremic Agents/therapeutic use , Cholesterol, LDL/blood , Treatment Outcome , Heart Disease Risk Factors , Proprotein Convertase 9
10.
G Ital Cardiol (Rome) ; 25(7): 530-540, 2024 Jul.
Article in Italian | MEDLINE | ID: mdl-38916469

ABSTRACT

Cardiovascular (CV) diseases account for over 4 million deaths every year in Europe and over 220 000 deaths in Italy, representing the leading cause of morbidity and mortality worldwide. The European Society of Cardiology (ESC) guidelines have visionary included in the at very high CV risk group patients without previous acute ischemic events, such as those with subclinical atherosclerosis, chronic coronary syndrome or peripheral arterial disease, familial hypercholesterolemia, diabetes mellitus with target organ damage or multiple associated risk factors, and those with high calculated CV risk score, recommending to consider them and to achieve the same LDL-cholesterol targets as for secondary prevention patients. The aim of this position paper is to provide an updated overview of ESC guidelines that focuses on these patient categories to raise awareness within the clinical community regarding CV risk reduction in this specific epidemiological context.


Subject(s)
Cardiovascular Diseases , Cholesterol, LDL , Heart Disease Risk Factors , Humans , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/etiology , Cholesterol, LDL/blood , Practice Guidelines as Topic , Italy , Secondary Prevention/methods , Europe , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy
11.
Cells ; 13(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38891115

ABSTRACT

The 9p21.3 genomic locus is a hot spot for disease-associated single-nucleotide polymorphisms (SNPs), and its strongest associations are with coronary artery disease (CAD). The disease-associated SNPs are located within the sequence of a long noncoding RNA ANRIL, which potentially contributes to atherogenesis by regulating vascular cell stress and proliferation, but also affects pancreatic ß-cell proliferation. Altered expression of a neighboring gene, CDKN2B, has been also recognized to correlate with obesity and hepatic steatosis in people carrying the risk SNPs. In the present study, we investigated the impact of 9p21.3 on obesity accompanied by hyperlipidemia in mice carrying a deletion of the murine ortholog for the 9p21.3 (Chr4Δ70/Δ70) risk locus in hyperlipidemic Ldlr-/-ApoB100/100 background. The Chr4Δ70/Δ70 mice showed decreased mRNA expression of insulin receptors in white adipose tissue already at a young age, which developed into insulin resistance and obesity by aging. In addition, the Sirt1-Ppargc1a-Ucp2 pathway was downregulated together with the expression of Cdkn2b, specifically in the white adipose tissue in Chr4Δ70/Δ70 mice. These results suggest that the 9p21.3 locus, ANRIL lncRNA, and their murine orthologues may regulate the key energy metabolism pathways in a white adipose tissue-specific manner in the presence of hypercholesterolemia, thus contributing to the pathogenesis of metabolic syndrome.


Subject(s)
Hypercholesterolemia , Insulin Resistance , Obesity , Animals , Obesity/genetics , Obesity/metabolism , Insulin Resistance/genetics , Hypercholesterolemia/genetics , Hypercholesterolemia/metabolism , Hypercholesterolemia/complications , Mice , Humans , Chromosomes, Human, Pair 9/genetics , Male , Gene Deletion , Genetic Loci , Mice, Inbred C57BL , Adipose Tissue, White/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
12.
Ter Arkh ; 96(5): 471-478, 2024 Jun 03.
Article in Russian | MEDLINE | ID: mdl-38829808

ABSTRACT

AIM: To evaluate the relationship of hypercholesterolemia (HCE) with clinical, instrumental, and laboratory parameters in osteoarthritis (OA) in a multicenter, cross-sectional study. MATERIALS AND METHODS: The study included 183 patients aged 40-75 years, with a confirmed diagnosis of stage I-III OA (ACR) of the knee joints, who signed an informed consent. The mean age was 55.6±10.7 years (40 to 75), body mass index was 29.3±6.3 kg/m2, and disease duration was 5 [1; 10] years. For each patient, a case record form was filled out, including anthropometric indicators, medical history, clinical examination data, an assessment of knee joint pain according to VAS, WOMAC, KOOS and comorbidities. All patients underwent standard radiography and ultrasound examination of the knee joints and laboratory tests. RESULTS: HCE was detected in 59% of patients. Depending on its presence or absence, patients were divided into two groups. Patients were comparable in body mass index, waist and hip measurement, and disease duration but differed significantly in age. Individuals with elevated total cholesterol levels had higher VAS pain scores, total WOMAC and its components, an overall assessment of the patient's health, a worse KOOS index, and ultrasound findings (reduced cartilage tissue). HCE patients showed high levels of cholesterol, low-density lipoproteins, triglycerides, STX-II, and COMP (p<0.05). However, after stratification by age, many initial intergroup differences became insignificant, and differences in the WOMAC pain score persisted. CONCLUSION: The results of the study confirmed the high prevalence of HCE in OA patients (59%). Patients with OA and increased total cholesterol have more intense pain in the knee joints.


Subject(s)
Hypercholesterolemia , Osteoarthritis, Knee , Humans , Middle Aged , Male , Female , Hypercholesterolemia/epidemiology , Hypercholesterolemia/complications , Cross-Sectional Studies , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/epidemiology , Osteoarthritis, Knee/etiology , Aged , Adult , Pain Measurement/methods , Russia/epidemiology , Knee Joint/physiopathology , Knee Joint/diagnostic imaging , Severity of Illness Index , Cholesterol/blood
13.
Coron Artery Dis ; 35(7): 577-583, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-38861193

ABSTRACT

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.


Subject(s)
Cholesterol, LDL , Coronary Artery Disease , Diet, Ketogenic , Disease Progression , Humans , Diet, Ketogenic/methods , Coronary Artery Disease/blood , Coronary Artery Disease/etiology , Cholesterol, LDL/blood , Male , Diet, Carbohydrate-Restricted/methods , Female , Computed Tomography Angiography/methods , Hypercholesterolemia/diet therapy , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Coronary Angiography/methods , Biomarkers/blood , Middle Aged , Adult
14.
Panminerva Med ; 66(2): 117-123, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38722673

ABSTRACT

BACKGROUND: Menopausal transition is a crucial step in the women's cardiovascular health, and the risk stratification in apparently health post-menopausal females has been rarely assessed. Heart ultrasonography, unusually performed in such subjects, would be able to detect initial signs of organ damage. We described the cardiovascular risk profile of non-diabetic post-menopausal women, evaluating how easily computed, biochemistry-derived scores were related to ultrasonographic measures of target organ damage. METHODS: We analyzed the characteristics of a cohort of two-hundred and seventy-three women consecutively referring to a prevention program of Azienda Ospedaliero-Universitaria Pisana (years 2017-2022) who underwent clinical evaluation, complete routine biochemical analyses with proxies of insulin resistance, heart and carotid ultrasonography. The cohort was further divided into four groups according to presence of isolated hypercholesterolemia (HC, 37%), isolated hypertension (HT, 5%), both HC/HT (38%), or none of them. RESULTS: In HC and HC/HT, LDL cholesterol was sharply above the recommended values (149 [134-171] mg/dL and 141 [123-159] mg/dL, respectively). E/e' ratio and left atrium size were augmented in HT women and further worsened in HT/HC, with an independent effect of hypertension (E/e' ß=0.055, P=0.013, left atrium volume ß=0.059, P=0.003). Presence of carotid plaques was independently linked to hypertension (ß=0.474, P=0.003). In HC and HC/HT, the Triglycerides-Glucose Index, a surrogate of insulin resistance, was higher than in the other classes (P=0.0013), and it was associated with E/A in HC and HT/HC, with a significative interaction (P=0.0004) with hypertension. Past hormone replacement therapy did not influence clinical, biochemical or echocardiographic parameters. CONCLUSIONS: Postmenopausal women display a high cardiovascular risk burden; a simple clinical and biochemistry screening would be advisable to identify and treat those more at risk. Cardiac ultrasonographic parameters were worse in hypertensive, hypercholesterolemic and insulin-resistant subjects, who may also deserve a deep and early instrumental characterization, especially when these conditions are associated.


Subject(s)
Cardiometabolic Risk Factors , Hypertension , Postmenopause , Humans , Female , Middle Aged , Hypertension/complications , Aged , Hypercholesterolemia/complications , Hypercholesterolemia/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Insulin Resistance , Blood Glucose/metabolism , Italy/epidemiology , Risk Assessment , Risk Factors , Biomarkers/blood , Echocardiography
15.
Clin Res Hepatol Gastroenterol ; 48(6): 102363, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703815

ABSTRACT

PURPOSE: This study aimed to explore the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and the development of new-onset gallbladder stone disease (GSD) and to identify factors that influence the occurrence of new-onset GSD in patients with MASLD. METHODS: In this retrospective case-control study, patients who underwent asymptomatic GSD screening during annual routine health check-ups at two hospitals in China between August 2017 and July 2022 were included. Patients with new-onset GSD and controls without GSD were matched 1:1 based on age, sex, race, occupation, diet, drinking habits, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels. RESULTS: The study comprised 1200 patients with new-onset GSD and 1200 controls without GSD. Patients with new-onset GSD had higher rates of MASLD (33.8% vs. 22.2 %, P < 0.001) and hypercholesterolemia (12.6% vs. 7.2 %, P < 0.001) compared to controls. Waist circumference (WC) (OR = 1.042, 95 % CI: 1.022-1.063, P < 0.001), high-density lipoprotein cholesterol (HDL-c) (OR = 0.048, 95 % CI: 0.037-0.062, P < 0.001), triglycerides (OR = 0.819, 95 % CI: 0.699-0.958, P = 0.013), and hypercholesterolemia (OR = 5.023, 95 % CI: 2.735-9.225, P < 0.001) were independently associated with new-onset GSD. Among patients with MASLD, WC (OR = 1.075, 95 % CI: 1.026-1.127, P = 0.003), total cholesterol (TC) (OR = 2.094, 95 % CI: 1.259-3.484, P = 0.004), HDL-c (OR = 0.088, 95 % CI: 0.054-0.142, P < 0.001), and low-density lipoprotein cholesterol (LDL-c) (OR = 4.056, 95 % CI: 2.669-6.163, P < 0.001) were independently associated with new-onset GSD. CONCLUSIONS: The findings indicate that hypercholesterolemia is independently associated with GSD. Among patients with MASLD, hypercholesterolemia also showed an independent association with GSD. Notably, this study is the first to identify serum LDL-c levels as potentially the most significant risk factor for GSD, highlighting that elevated LDL-c could serve as an important indicator for individuals with MASLD.


Subject(s)
Cholesterol, LDL , Humans , Male , Female , Middle Aged , Case-Control Studies , Retrospective Studies , Cholesterol, LDL/blood , Adult , Gallstones/complications , Gallstones/etiology , Fatty Liver/complications , Fatty Liver/etiology , Fatty Liver/blood , Risk Factors , Hypercholesterolemia/complications
16.
Curr Atheroscler Rep ; 26(8): 435-449, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38814418

ABSTRACT

PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.


Subject(s)
Cholesterol , Dementia, Vascular , Hypercholesterolemia , Humans , Dementia, Vascular/etiology , Dementia, Vascular/epidemiology , Dementia, Vascular/metabolism , Hypercholesterolemia/complications , Hypercholesterolemia/epidemiology , Risk Factors , Cholesterol/metabolism , Cholesterol/blood
17.
Sci Rep ; 14(1): 8407, 2024 04 10.
Article in English | MEDLINE | ID: mdl-38600230

ABSTRACT

Elevated remnant cholesterol (RC) is considered a risk factor for atherosclerotic cardiovascular disease, but the evidence on this association applies to the Chinese population with hypertension is limited. We aimed to explore the association between RC levels and carotid plaque in old adults with hypertension. 8523 hypertensive patients aged ≥ 60 years with serum lipids and carotid ultrasonography data were included in this community-based screening. Fasting RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDLC). The associations of RC levels with carotid plaque risk were evaluated using Logistic regression and restricted cubic spline models. Carotid plaque was screened in 4821 (56.56%) subjects. After multivariable-adjusted, RC was significantly related to carotid plaque [Odd ratio (OR)] = 1.043 per 0.1 mmol/L increase, 95% confidence interval (CI): 1.030-1.056). The highest versus the lowest quartile of RC was 1.928 (1.673-2.223) for carotid plaque. A nonlinear association was found between serum RC levels and the risk of carotid plaque (P for nonlinearity < 0.001). Moreover, an RC > 0.78 mmol/L differentiated patients at a higher risk of carotid plaque compared to those at lower concentrations, regardless of whether LDLC was on target at 2.59 mmol/L. In old adults with hypertension, elevated RC was positively associated with carotid plaque, independent of LDLC and other conventional risk factors.


Subject(s)
Atherosclerosis , Hypercholesterolemia , Hypertension , Plaque, Atherosclerotic , Adult , Humans , Cholesterol , Hypertension/complications , Hypertension/epidemiology , Carotid Arteries , Atherosclerosis/complications , Risk Factors , Hypercholesterolemia/complications , China/epidemiology
18.
Eur J Med Res ; 29(1): 237, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622622

ABSTRACT

BACKGROUND: Atherosclerotic vascular diseases are a leading global cause of morbidity and mortality. Dyslipidemia, a major modifiable risk factor for cardiovascular disease, remains poorly understood among adult cardiac patients in in the study area. This study aims to determine the prevalence of dyslipidemia and identify associated factors in this population. METHODS: Hospital-based comparative cross-sectional study was conducted from May to August 2021. A total of 319 participants (153 cardiac cases, 166 healthy controls, aged ≥ 18) were included in the study. Socio-demographic, anthropometric, behavioral, and clinical data were collected using the WHO STEPS survey instrument through systematic sampling. Overnight fasting blood samples were obtained, and serum lipid profiles were analyzed using a COBAS 6000 analyzer. Data were analyzed with SPSS version 20.0, employing bivariable and multivariable logistic regression. Statistical significance was set at p < 0.05. RESULTS: The overall prevalence of dyslipidemia, encompassing at least one lipid abnormality, was 80.3% among 256 participants. Among cardiac cases, the prevalence rates were as follows: 72.5% for low HDL-cholesterol, 12.4% for hypercholesterolemia, 9.8% for elevated LDL-cholesterol, and 30.1% for hypertriglyceridemia. In controls, corresponding rates were 69.9%, 9.6%, 7.2%, and 32.5%. Significant factors linked to low HDL- cholesterol were female gender (AOR: 2.8, 95% CI 1.7-4.7) and obesity (AOR: 2.8, 95% CI 1.1-7.5). Abdominal obesity was associated with hypercholesterolemia (AOR: 5.2, 95% CI 1.9-14.3) and elevated LDL-cholesterol (AOR: 5.1, 95% CI 1.6-15.8). High blood pressure, overweight, and abdominal obesity were significantly linked to hypertriglyceridemia (p < 0.05). CONCLUSION: Dyslipidemia was high among the study participants. Overweight, obesity, central adiposity, and high blood pressure were significantly associated with dyslipidemia in cardiac patients. This alarms the need for lipid profile assessment for patients periodically, with treatment follow-up to monitor any rising patterns and cardiovascular-related risks.


Subject(s)
Dyslipidemias , Hypercholesterolemia , Hypertension , Hypertriglyceridemia , Adult , Humans , Female , Male , Hypercholesterolemia/complications , Hypercholesterolemia/epidemiology , Overweight/complications , Overweight/epidemiology , Cross-Sectional Studies , Obesity, Abdominal/complications , Obesity, Abdominal/epidemiology , Dyslipidemias/epidemiology , Dyslipidemias/complications , Risk Factors , Obesity/complications , Obesity/epidemiology , Hypertriglyceridemia/complications , Prevalence , Hospitals , Cholesterol , Lipids
19.
G Ital Cardiol (Rome) ; 25(5): 318-326, 2024 May.
Article in Italian | MEDLINE | ID: mdl-38639122

ABSTRACT

Over the last decade, several innovative therapeutic options have been developed and marketed for the management of hypercholesterolemia. However, the impossibility of a contextual update of international guidelines and the limits imposed by national regulatory authorities do not allow the use of these treatments in many patients, in particular in those at higher cardiovascular risk. Real-world studies show that the use of lipid-lowering therapies is inadequate even among patients at higher cardiovascular risk, with only 20% achieving recommended low-density lipoprotein cholesterol (LDL-C) levels and the use of combination therapies implemented in only 24% of patients. This review aims to highlight the benefits of an approach based on combination therapy and to propose a therapeutic algorithm that includes oral combination therapy, where necessary also in triple association (statin, ezetimibe and bempedoic acid), as an initial approach based on the most favorable cost-effectiveness ratio for patients at higher cardiovascular risk and the use of injectable anti-proprotein convertase subtilisin/kexin 9 therapies if the recommended LDL-C goal is not achieved.


Subject(s)
Anticholesteremic Agents , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypercholesterolemia , Humans , Cholesterol, LDL , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/chemically induced , Risk Factors , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Ezetimibe/therapeutic use , Proprotein Convertase 9 , Heart Disease Risk Factors , Anticholesteremic Agents/therapeutic use
20.
Medicina (Kaunas) ; 60(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38674198

ABSTRACT

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Paraneoplastic Syndromes , Humans , Male , Retrospective Studies , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/complications , Female , Paraneoplastic Syndromes/epidemiology , Paraneoplastic Syndromes/mortality , Middle Aged , Liver Neoplasms/mortality , Liver Neoplasms/epidemiology , Liver Neoplasms/complications , Aged , Prevalence , Adult , Survival Analysis , Hypercholesterolemia/epidemiology , Hypercholesterolemia/complications , Hypoglycemia/epidemiology , Hypoglycemia/complications , Polycythemia/epidemiology , Polycythemia/complications , Aged, 80 and over , Thrombocytosis/epidemiology , Thrombocytosis/complications
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