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1.
Ann Lab Med ; 43(1): 29-37, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36045054

RESUMO

Background: High LDL-cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is considered an important therapeutic target. It can be measured directly or calculated from the results of other lipid tests. The Friedewald formula is the most widely used formula for calculating LDL-C. We modified the Friedewald formula for a more accurate and practical estimation of LDL-C. Methods: Datasets, including measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-C concentrations were collected and assigned to derivation and validation sets. The datasets were further divided into five groups based on triglyceride concentrations. In the modified formula, LDL-C was defined as total cholesterol - HDL-cholesterol - (triglyceride/adjustment factor). For each group, the adjustment factor that minimized the difference between measured LDL-C and calculated LDL-C using modified formula was obtained. For validation, measured LDL-C and LDL-C calculated using the modified formula (LDL-CM), Friedewald formula (LDL-CF), Martin-Hopkins formula (LDL-CMa), and Sampson formula (LDL-CS) were compared. Results: In the derivation set, the adjustment factors were 4.7, 5.9, 6.3, and 6.4 for the groups with triglyceride concentrations <100, 101-200, 201-300, and >300 mg/dL, respectively. In the validation set, the coefficient of determination (R2) between measured and calculated LDL-C was higher for LDL-CM than for LDL-CF (R2=0.9330 vs. 0.9206). The agreement according to the National Cholesterol Education Program Adult Treatment Panel III classification of LDL-C was 86.36%, 86.08%, 86.82%, and 86.15% for LDL-CM, LDL-CF, LDL-CMa, and LDL-CS, respectively. Conclusions: We proposed a practical, improved LDL-C calculation formula by applying different factors depending on the triglyceride concentration.


Assuntos
Doenças Cardiovasculares , Hipercolesterolemia , Hiperlipidemias , Adulto , HDL-Colesterol , LDL-Colesterol , Humanos , Triglicerídeos
2.
Curr Probl Cardiol ; 48(1): 101421, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167221

RESUMO

Dyslipidemia is associated with increased cancer risk. However, the prognostic value of visit-to-visit lipid variability (VVLV) is unexplored in this regard. To investigate the associations between the VVLV and the risk of incident cancer, we conducted a retrospective cohort study on adult patients attending a family medicine clinic in Hong Kong during 2000-2003, excluding those with <3 tests for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and total cholesterol (TC) each, those with prior cancer diagnosis, and those with <1 year of follow-up. Visit-to-visit LDL-C, HDL-C, TC, and triglycerides variabilities were measured by the coefficient of variation (CV). Patients were followed up until 31st December 2019 for the primary outcome of incident cancer. Altogether, 69,186 patients were included (26,679 males (38.6%); mean age 60 ± 13 years; mean follow-up 16 ± 3 years); 7958 patients (11.5%) had incident cancer. Higher variability of LDL-C, HDL-C, TC, and TG was associated with higher risk of incident cancer. Patients in the third tercile of the CV of LDL-C (adjusted hazard ratio (aHR) against first tercile 1.06 [1.00, 1.12], P = 0.049), HDL-C (aHR 1.37 [1.29, 1.44], P< 0.001), TC (aHR 1.10 [1.04, 1.17], P = 0.001), and TG (aHR 1.11 [1.06, 1.18], P < 0.001) had the highest risks of incident cancer. Among these, only HDL-C variability remained associated with the risk of incident cancer in users of statins/fibrates. To conclude, higher VVLV was associated with significantly higher long-term risks of incident cancer. VVLV may be a clinically useful tool for cancer risk stratification.


Assuntos
Neoplasias , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , LDL-Colesterol , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , HDL-Colesterol , Triglicerídeos , Neoplasias/diagnóstico , Neoplasias/epidemiologia
3.
Environ Res ; 216(Pt 3): 114639, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36309217

RESUMO

Clinical laboratory in hospital can produce amounts of health data every day. The purpose of this study was to mine biomarkers from clinical laboratory big data associated with the air pollution health risk assessment using clinical records. 13, 045, 629 clinical records of all 27 routine laboratory tests in Changsha Central Hospital, including ALB, TBIL, ALT, DBIL, AST, TP, UREA, UA, CREA, GLU, CK, CKMB, LDL-C, TG, TC, HDL-C, CRP, WBC, Na, K, Ca, Cl, APTT, PT, FIB, TT, RBC and those daily air pollutants concentration monitoring data of Changsha, including PM2.5, PM10, SO2, NO2, CO, and O3 from 2014 to 2016, were retrieved. The moving average method was used to the biological reference interval was established. The tests results were converted into daily abnormal rate. After data cleaning, GAM statistical model construction and data analysis, a concentration-response relationship between air pollutants and daily abnormal rate of routine laboratory tests was observed. Our study found that PM2.5 had a stable association with TP (lag07), ALB (lag07), ALT (lag07), AST (lag07), TBIL (lag07), DBIL (lag07), UREA (lag07), CREA (lag07), UA (lag07), CK (lag 06), GLU (lag07), WBC (lag07), Cl (lag07) and Ca (lag07), (P < 0.05); O3 had a stable association with AST (lag01), CKMB (lag06), TG (lag07), TC (lag05), HDL-C (lag07), K (lag05) and RBC (lag07) (P < 0.05); CO had a stable association with UREA (lag07), Na (lag7) and PT (lag07) (P < 0.05); SO2 had a stable association with TP (lag07) and LDL-C (lag0) (P < 0.05); NO2 had a stable association with APTT (lag7) (P < 0.05). These results showed that different air pollutants affected different routine laboratory tests and presented different pedigrees. Therefore, biomarkers mined from routine laboratory tests may potentially be used to low-cost assess the health risks associated with air pollutants.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Dióxido de Nitrogênio/análise , LDL-Colesterol , Poluição do Ar/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Medição de Risco , Biomarcadores/análise , Material Particulado/análise , Ureia/análise , China
4.
Pediatr Blood Cancer ; 70(1): e30034, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36326745

RESUMO

BACKGROUND: Childhood cancer survivors (CCS) have increased risk of premature cardiovascular disease. Whether they respond similarly to lifestyle changes for elevated blood pressure (BP), body mass index (BMI), and dyslipidemia to those without history of childhood cancer is unknown. PROCEDURE: This retrospective cohort study included CCS and 3:1 age- and sex-matched controls treated at Boston Children's Hospital Preventive Cardiology (2010-2019) using lifestyle management based on National Heart, Lung, and Blood Institute (NHLBI) guidelines. Change in BMI, BP, and lipids were analyzed. RESULTS: We included 52 CCS and 162 controls with a median age of approximately 16 years. More CCS (84.3%) had elevated baseline fasting triglycerides (TG) than controls (49.4%) (p < .001). More CCS (62.5%) also had abnormal baseline high-density lipoprotein cholesterol (HDL-C) compared to controls (35.2%) (p = .001). Baseline BMI, BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were similar between groups. Over 15 weeks [IQR: 10.5-26], CCS had greater decrease in TG than controls (72.5 vs. 17 mg/dl decrease, p = .095). BP improved in 5% of CCS versus 38% of controls (p = .008). For both, BMI, TC, LDL-C, and HDL-C remained stable. CCS with stem cell transplantation (SCT) had a TC increase of 5% (6 mg/dl) compared to a decrease of 9% (19 mg/dl) among CCS without SCT (p = .02). CONCLUSIONS: CCS demonstrated similar improvement in lipids, but impaired BP lowering in response to lifestyle management compared to controls. Further prospective studies are needed to determine if earlier pharmaceutical treatment is warranted in this higher risk population and for the long-term risk reductions of these approaches.


Assuntos
Sobreviventes de Câncer , Dislipidemias , Hipertensão , Neoplasias , Criança , Humanos , Adolescente , LDL-Colesterol , Estudos Retrospectivos , Pressão Sanguínea , Lipídeos , Neoplasias/terapia , Dislipidemias/etiologia , Dislipidemias/terapia , HDL-Colesterol , Estilo de Vida , Aconselhamento , Triglicerídeos
5.
Curr Opin Nephrol Hypertens ; 32(1): 27-34, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36250471

RESUMO

PURPOSE OF REVIEW: Lipid disorder is a prevalent complication in kidney transplant recipients (KTRs) resulting in cardiovascular disease (CVD), which influences on patient outcomes. Immunosuppressive therapy demonstrated the major detrimental effects on metabolic disturbances. This review will focus on the effect of immunosuppressive drugs, lipid-lowering agents with current management, and future perspectives for lipid management in KTRs. RECENT FINDINGS: The main pathogenesis of hyperlipidemia indicates an increase in lipoprotein synthesis whilst the clearance of lipid pathways declines. Optimization of immunosuppression is a reasonable therapeutic strategy for lipid management regarding immunologic risk. Additionally, statin is the first-line lipid-lowering drug, followed by a combination with ezetimibe to achieve the low-density lipoprotein cholesterol (LDL-C) goal. However, drug interaction between statins and immunosuppressive medications should be considered because both are mainly metabolized through cytochrome P450 3A4. The prevalence of statin toxicity was significantly higher when concomitantly prescribed with cyclosporin, than with tacrolimus. SUMMARY: To improve cardiovascular outcomes, LDL-C should be controlled at the target level. Initiation statin at a low dose and meticulous titration is crucial in KTRs. Novel therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which is highly effective in reducing LDL-C and cardiovascular complications, and might prove to be promising therapy for KTRs with statin resistance or intolerance.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Pró-Proteína Convertase 9/metabolismo , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Anticolesterolemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia
6.
Gene ; 849: 146908, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36167182

RESUMO

Familial hypercholesterolemia (FH) is a prevalent autosomal genetic disease associated with increased risk of early cardiovascular events and death due to chronic exposure to very high levels of low-density lipoprotein cholesterol (LDL-c). Pathogenic variants in the coding regions of LDLR, APOB and PCSK9 account for most FH cases, and variants in non-coding regions maybe involved in FH as well. Variants in the upstream region of LDLR, APOB and PCSK9 were screened by targeted next-generation sequencing and their effects were explored using in silico tools. Twenty-five patients without pathogenic variants in FH-related genes were selected. 3 kb upstream regions of LDLR, APOB and PCSK9 were sequenced using the AmpliSeq (Illumina) and Miseq Reagent Nano Kit v2 (Illumina). Sequencing data were analyzed using variant discovery and functional annotation tools. Potentially regulatory variants were selected by integrating data from public databases, published data and context-dependent regulatory prediction score. Thirty-four single nucleotide variants (SNVs) in upstream regions were identified (6 in LDLR, 15 in APOB, and 13 in PCSK9). Five SNVs were prioritized as potentially regulatory variants (rs934197, rs9282606, rs36218923, rs538300761, g.55038486A > G). APOB rs934197 was previously associated with increased rate of transcription, which in silico analysis suggests that could be due to reducing binding affinity of a transcriptional repressor. Our findings highlight the importance of variant screening outside of coding regions of all relevant genes. Further functional studies are necessary to confirm that prioritized variants could impact gene regulation and contribute to the FH phenotype.


Assuntos
Hiperlipoproteinemia Tipo II , Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/genética , LDL-Colesterol/genética , Receptores de LDL/genética , Brasil , Mutação , Hiperlipoproteinemia Tipo II/genética , Fenótipo , Apolipoproteínas B/genética , Nucleotídeos
7.
Eur J Prev Cardiol ; 28(18): 2001-2009, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33624058

RESUMO

AIM: The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). METHODS AND RESULTS: Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. CONCLUSION: This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Colesterol , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Infarto do Miocárdio/prevenção & controle
8.
Lipids Health Dis ; 21(1): 114, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324160

RESUMO

BACKGROUND: Although potent lipid-lowering therapies are available, patients commonly fall short of recommended low-density lipoprotein cholesterol (LDL-C) levels. The aim of this study was to examine the relationship between familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] and LDL-C goal attainment, as well as the prevalence and severity of coronary artery disease (CAD). Moreover, we characterized patients failing to meet recommended LDL-C goals. METHODS: We performed a cross-sectional analysis in a cohort of patients undergoing cardiac catheterization. Clinical FH was determined by the Dutch Clinical Lipid Network Score, and Lp(a) ≥ 50 mg/dL (≈ 107 nmol/L) was considered elevated. RESULTS: A total of 838 participants were included. Overall, the prevalence of CAD was 72%, and 62% received lipid-lowering treatment. The prevalence of clinical FH (probable and definite FH) was 4%, and 19% had elevated Lp(a) levels. With 35%, LDL-C goal attainment was generally poor. Among the participants with clinical FH, none reached their LDL-C target. Among patients with elevated Lp(a), LDL-C target achievement was only 28%. The prevalence and severity of CAD were higher in participants with clinical FH (86% prevalence) and elevated Lp(a) (80% prevalence). CONCLUSION: Most participants failed to meet their individual LDL-C goals according to the ESC 2016 and 2019 guidelines. In particular, high-risk patients with clinical FH or elevated Lp(a) rarely met their target for LDL-C. The identification of these patients and more intense treatment approaches are crucial for the improvement of CAD primary and secondary prevention.


Assuntos
Doença da Artéria Coronariana , Hiperlipoproteinemia Tipo II , Humanos , LDL-Colesterol , Estudos Transversais , Objetivos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/complicações , Fatores de Risco
9.
J Transl Med ; 20(1): 502, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329474

RESUMO

BACKGROUND: The genetic architecture underlying Familial Hypercholesterolemia (FH) in Middle Eastern Arabs is yet to be fully described, and approaches to assess this from population-wide biobanks are important for public health planning and personalized medicine. METHODS: We evaluate the pilot phase cohort (n = 6,140 adults) of the Qatar Biobank (QBB) for FH using the Dutch Lipid Clinic Network (DLCN) criteria, followed by an in-depth characterization of all genetic alleles in known dominant (LDLR, APOB, and PCSK9) and recessive (LDLRAP1, ABCG5, ABCG8, and LIPA) FH-causing genes derived from whole-genome sequencing (WGS). We also investigate the utility of a globally established 12-SNP polygenic risk score to predict FH individuals in this cohort with Arab ancestry. RESULTS: Using DLCN criteria, we identify eight (0.1%) 'definite', 41 (0.7%) 'probable' and 334 (5.4%) 'possible' FH individuals, estimating a prevalence of 'definite or probable' FH in the Qatari cohort of ~ 1:125. We identify ten previously known pathogenic single-nucleotide variants (SNVs) and 14 putatively novel SNVs, as well as one novel copy number variant in PCSK9. Further, despite the modest sample size, we identify one homozygote for a known pathogenic variant (ABCG8, p. Gly574Arg, global MAF = 4.49E-05) associated with Sitosterolemia 2. Finally, calculation of polygenic risk scores found that individuals with 'definite or probable' FH have a significantly higher LDL-C SNP score than 'unlikely' individuals (p = 0.0003), demonstrating its utility in Arab populations. CONCLUSION: We design and implement a standardized approach to phenotyping a population biobank for FH risk followed by systematically identifying known variants and assessing putative novel variants contributing to FH burden in Qatar. Our results motivate similar studies in population-level biobanks - especially those with globally under-represented ancestries - and highlight the importance of genetic screening programs for early detection and management of individuals with high FH risk in health systems.


Assuntos
Hiperlipoproteinemia Tipo II , Pró-Proteína Convertase 9 , Adulto , Humanos , Pró-Proteína Convertase 9/genética , Bancos de Espécimes Biológicos , LDL-Colesterol , Fenótipo , Hiperlipoproteinemia Tipo II/complicações , Receptores de LDL , Mutação
10.
Int J Clin Pract ; 2022: 6130774, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349053

RESUMO

Objective: Systemic lupus erythematosus (SLE) is a relatively common rheumatic disease in children. The characteristics of blood lipid metabolism in children with LN are little reported. This study aimed to explore the relationship between blood lipid profiles and the risk of lupus nephritis (LN) in children. Methods: A total of 134 children with newly diagnosed SLE were divided into LN and non-LN groups according to pathological renal biopsy results. Clinical manifestations and blood lipid profiles were analyzed and compared between the two groups, and the relationships between blood lipid profiles and risk of LN were evaluated. Results: The positivity rate of an anti-dsDNA antibody and an SLE disease activity index (SLEDAI) were significantly increased, and C3 and C4 levels were significantly reduced in the LN compared with the non-LN group. The overall incidence of dyslipidemia was 79.9%, with a significantly high incidence in the LN group compared with the non-LN group. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very LDLC (VLDL-C) were all higher in the LN group than those in the non-LN group. However, there was no significant difference in high-density lipoprotein cholesterol (HDL-C) between the two groups. The blood lipid levels were positively correlated with 24-hour urine protein quantification, urea, creatinine, uric acid, urinary IgG, urinary microalbumin, urinary transferrin, urinary α1 microglobulin, and urinary N-acetyl glucosidase, respectively. Receiver-operating characteristic curves showed that combined detection of TC, TG, LDL-C, and VLDL-C had higher discrimination capacity than that in individual measures. Additionally, increased TC was independently associated with the occurrence of LN. Conclusions: Children with LN have significant dyslipidemia. High levels of TC, TG, LDL-C, and VLDL-C are closely related to the occurrence of pLN. Clinical attention should be paid to monitoring and managing blood lipid profiles in children with LN.


Assuntos
Dislipidemias , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Criança , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/urina , LDL-Colesterol , Biomarcadores , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Triglicerídeos , Dislipidemias/epidemiologia
11.
Cardiovasc Diabetol ; 21(1): 255, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36419118

RESUMO

BACKGROUND: Individuals diagnosed with and treated for type 1 diabetes (T1D) have increased risk of micro- and macrovascular disease and excess mortality. Improving cardiovascular (CV) risk factors in individuals with T1D is known to reduce diabetes- related CV complications. AIM: To examine time trends in CV risk factor levels and CV-protective treatment patterns. Additionally, examine incidence rates of diabetes-related CV complications in relation to exposure CV-protective treatment. METHODS: We analysed records from 41,630 individuals with T1D, registered anytime between 1996 and 2017 in a nationwide diabetes register. We obtained CV risk factor measurements (2010-2017), CV-protective drug profiles (1996-2017) and CV complication history (1977-2017) from additional nationwide health registers. RESULTS: From 2010 to 2017 there were decreasing levels of HbA1c, LDL-C, and blood pressure. Decreasing proportion of smokers, individuals with glycaemic dysregulation (HbA1c ≥ 58 mmol/mol), dyslipidaemia (LDL-C > 2.6 mmol/l), and hypertension (≥ 140/85 mmHg). Yet, one fifth of the T1D population by January 1st, 2017 was severely dysregulated (HbA1c > 75 mmol/mol). A slight increase in levels of BMI and urinary albumin creatinine ratio and a slight decrease in estimated glomerular filtration rate (eGFR) levels was observed. By January 1st, 2017, one fourth of the T1D population had an eGFR < 60 ml/min/1.73 m2. The proportion of the T1D population redeeming lipid-lowering drugs (LLDs) increased from 5% in 2000 to 30% in 2010 followed by a plateau and then a decline. The proportion of the T1D population redeeming antihypertensive drugs (AHDs) increased from 28% in 1996 to 42% in 2010 followed by a tendency to decline. Use of LLDs was associated with lower incidence of micro- and macrovascular complications, while use of AHDs had higher incidence of CVD and CKD, when compared to non-use and discontinued use, respectively. CONCLUSION: Improvements were seen in CV risk factor control among individuals with T1D in Denmark between 2010 and 2017. However, there is clearly a gap between current clinical guidelines and clinical practice for CV risk management in T1D. Action is needed to push further improvements in CV risk control to reduce CVD and the related excess mortality.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Anti-Hipertensivos/uso terapêutico , Gestão de Riscos , Hipolipemiantes
12.
Genome Med ; 14(1): 132, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36419110

RESUMO

BACKGROUND: Dyslipidemia is a major risk factor for cardiovascular disease, and diabetes impacts the lipid metabolism through multiple pathways. In addition to the standard lipid measurements, apolipoprotein concentrations provide added awareness of the burden of circulating lipoproteins. While common genetic variants modestly affect the serum lipid concentrations, rare genetic mutations can cause monogenic forms of hypercholesterolemia and other genetic disorders of lipid metabolism. We aimed to identify low-frequency protein-altering variants (PAVs) affecting lipoprotein and lipid traits. METHODS: We analyzed whole-exome (WES) and whole-genome sequencing (WGS) data of 481 and 474 individuals with type 1 diabetes, respectively. The phenotypic data consisted of 79 serum lipid and apolipoprotein phenotypes obtained with clinical laboratory measurements and nuclear magnetic resonance spectroscopy. RESULTS: The single-variant analysis identified an association between the LIPC p.Thr405Met (rs113298164) and serum apolipoprotein A1 concentrations (p=7.8×10-8). The burden of PAVs was significantly associated with lipid phenotypes in LIPC, RBM47, TRMT5, GTF3C5, MARCHF10, and RYR3 (p<2.9×10-6). The RBM47 gene is required for apolipoprotein B post-translational modifications, and in our data, the association between RBM47 and apolipoprotein C-III concentrations was due to a rare 21 base pair p.Ala496-Ala502 deletion; in replication, the burden of rare deleterious variants in RBM47 was associated with lower triglyceride concentrations in WES of >170,000 individuals from multiple ancestries (p=0.0013). Two PAVs in GTF3C5 were highly enriched in the Finnish population and associated with cardiovascular phenotypes in the general population. In the previously known APOB gene, we identified novel associations at two protein-truncating variants resulting in lower serum non-HDL cholesterol (p=4.8×10-4), apolipoprotein B (p=5.6×10-4), and LDL cholesterol (p=9.5×10-4) concentrations. CONCLUSIONS: We identified lipid and apolipoprotein-associated variants in the previously known LIPC and APOB genes, as well as PAVs in GTF3C5 associated with LDLC, and in RBM47 associated with apolipoprotein C-III concentrations, implicated as an independent CVD risk factor. Identification of rare loss-of-function variants has previously revealed genes that can be targeted to prevent CVD, such as the LDL cholesterol-lowering loss-of-function variants in the PCSK9 gene. Thus, this study suggests novel putative therapeutic targets for the prevention of CVD.


Assuntos
Doenças Cardiovasculares , Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/genética , Sequenciamento Completo do Exoma , LDL-Colesterol/genética , Apolipoproteína C-III/genética , Apolipoproteínas/genética , Apolipoproteínas B/genética , Proteínas de Ligação a RNA/genética
13.
J Cardiovasc Pharmacol Ther ; 27: 10742484221138284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420979

RESUMO

OBJECTIVE: In primary hypercholesterolemia many people treated with statins do not reach their plasma LDL-C goals and are at increased risk of cardiovascular disease (CVD). This study aimed to evaluate efficacy and safety of a new fixed-dose combination (FDC) formulation of rosuvastatin/ezetimibe (R/E) in this population. METHODS: This was a multicenter, multinational, randomized, double-blind, double-dummy, active-controlled, parallel-arm study of FDC R/E in people with primary hypercholesterolemia at very high risk (VHR) or high risk (HR) of CVD, inadequately controlled with 20 mg or 10 mg stable daily dose of rosuvastatin or equipotent dose of another statin. The primary objective was to demonstrate superiority of FDC R/E versus rosuvastatin monotherapy uptitrated to 40 mg (R40) or 20 mg (R20) in reduction of LDL-C after 6 weeks. RESULTS: Randomized VHR participants (n = 244) were treated with R40, R40/E10, or R20/E10; randomized HR participants (n = 208) received R10/E10 or R20. In VHR participants, superiority of R40/E10 and R20/E10 versus R40 was demonstrated on LDL-C percent change from baseline to Week 6 with least squares mean differences (LSMD) of -19.66% (95% CI: -29.48% to -9.84%; P < .001) and -12.28% (95% CI: -22.12% to -2.44%; P = .015), respectively. In HR participants, superiority of R10/E10 over R20 was not demonstrated (LSMD -5.20%; 95% CI: -15.18% to 4.78%; P = .306), despite clinically relevant LDL-C reduction with R10/E10. No unexpected safety findings were reported. CONCLUSIONS: The results from this study suggest that R/E FDCs improve LDL-C reduction and goal achievement in people with primary hypercholesterolemia inadequately controlled with statins and at VHR/HR of CVD.


Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Humanos , Ezetimiba/uso terapêutico , Rosuvastatina Cálcica/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamento farmacológico , LDL-Colesterol , Doenças Cardiovasculares/tratamento farmacológico
14.
Medicine (Baltimore) ; 101(46): e31933, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401418

RESUMO

Sleep disturbances are associated with cold hypersensitivity (CH) and characterized by excessive cold sensation in specific body parts and cold thermal discomfort. This study investigated the effects of short-term sleep restriction followed by a recovery phase on subjective health status, inflammation, and lipid metabolism in different types of CH. A total of 118 healthy adults aged 35 to 44 years without sleep disturbances were enrolled. Participants underwent 4-hour sleep restrictions per day for 3 days at a hospital and then returned to their daily lives for 4 days of rest. CH was assessed using a structured questionnaire with eight characteristic symptoms. A questionnaire and blood tests were administered baseline, after sleep restriction, and follow-up to assess cortisol, lipid profiles, and self-reported stress and quality of life (QOL). Participants were divided into CH (44.1%) and non-CH (55.9%) groups. The CH group showed increased stress, impaired QOL, and decreased low-density lipoprotein-cholesterol (LDL-C) levels compared to the non-CH group after sleep restriction. The variance for QOL (effect size = 0.07), subjective stress (effect size = 0.053), and LDL-C (effect size = 0.029) among time points depended on the group. Short-term sleep restriction was associated with deterioration of subjective health and reduced lipid metabolism; such changes were more evident in the CH group. Our findings suggest the need to consider an individual's CH status to assess the clinical risk associated with insufficient sleep.


Assuntos
Qualidade de Vida , Adulto , Humanos , LDL-Colesterol , Metabolismo dos Lipídeos , Sono , Privação do Sono
15.
Front Endocrinol (Lausanne) ; 13: 1014670, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407321

RESUMO

Objective: This meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy of probiotics in the treatment of metabolic-associated fatty liver disease (MAFLD) mainly in terms of liver function, glucose and lipid metabolism, and inflammation. Methods: RCTs were searched on PubMed, Web of Science, Embase, and the Cochrane Library until June 2022. A meta-analysis was performed on the therapeutic efficacy of probiotics on liver function, glucose and lipid metabolism, and inflammatory biomarkers by using RevMan 5.4 software. Results: A total of 772 patients from 15 studies were included in the analysis. The methodological quality varied across studies. We found that adding probiotic therapies could reduce the levels of alanine aminotransferase [mean difference (MD): -11.76 (-16.06, -7.46), p < 0.00001], aspartate aminotransferase (MD: -9.08 (-13.60, -4.56), p < 0.0001], γ-glutamyltransferase [MD: -5.67 (-6.80, -4.54), p < 0.00001] and homeostasis model assessment-insulin resistance [MD: -0.62 (-1.08, -0.15), p = 0.01], in patients with MAFLD compared with those in control individuals. However, there was no statistically significant improvement in the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, C-reactive protein and tumor necrosis factor α among patients with MAFLD. Subgroup analyses showed that other key factors, such as age, participants' baseline body mass index, and the duration of intervention, may influence probiotic therapy outcomes. Conclusion: There is promising evidence that probiotic supplementation can reduce liver enzyme levels and regulate glycometabolism in patients with MAFLD. Further rigorous and long-term trials exploring these novel therapeutic perspectives are warranted to confirm these results.


Assuntos
Hepatopatias , Probióticos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Probióticos/uso terapêutico , LDL-Colesterol , Glucose , Metaboloma
17.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(4): 341-347, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36414559

RESUMO

Objective: To investigate the effects of 7-week swimming exercise with different loads on the improvement of liver lipid metabolism in mice with alcoholic fatty liver disease (AFLD) and its relationship with the regulation of miR-34a/PPARα. Methods: Fifty male KM mice were randomly divided into control group (K, n=10) and alcoholic fatty liver group (AFLD, n=40). The AFLD model was constructed after feeding with 50% alcohol for 7 weeks with 1 d rest per week. After successful model construction, the mice were divided into a model group (M), a 30-min swimming exercise group (LE), a 60-min swimming exercise group (ME), and a 90-min loaded swimming exercise group (HE, 5% of body mass as tail lead load), with 10 mice in each group, for a total of 7 weeks of intervention. After completion, the serum and liver tissues were collected, the liver index, visceral fat ratio, hepatocyte injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT), total cholesterol (TC), triglyceride (TG), and high/low density lipoprotein cholesterol (H/LDL-C) content were measured; HE staining was used to observe the changes in liver structure, Western blot was used to detect the protein levels of PPARα, FAS and TNF-α in liver tissues, and mRNA expression profiles were analyzed by sequencing After RT-PCR, the mRNA expressions of miR-34a, PPARα, FAS, TNF-α and CPT-1 were verified. Results: Compared with K group, the hepatic cord disorder, focal lipid vacuum, obvious lipid droplet vacuolation, abnormal ectopic nucleus were observed in AFLD group ; liver function was decreased significantly. Compared with the M group, the liver functions of the ME and HE groups were improved significantly, the serum levels of TG, TC and LDL-C were decreased, while the HDL-C level was increased (P<0.01 or P<0.05), and the liver index and visceral fat ratio were decreased (P< 0.01 or P<0.05), the focal lipid droplet degeneration of hepatocytes was decreased, and the structure of the hepatic cord was clearer; and the ME group showed a more significant intervention effect. Compared with the M group, the expression levels of PPARα protein in the liver tissues of the LE, ME, and HE groups were increased, while the protein expression levels of FAS and TNF-α were decreased (P<0.01 or P<0.05). Based on Illumina high-throughput sequencing and mRNA differential expression analysis, there are 38 differentially expressed genes in the PPARα pathway, including 9 up-regulated genes and 29 down-regulated genes, which are involved in liver fatty acid oxidation, lipid metabolism, and apoptosis inhibition. Compared with group M, the gene levels of miR-34a, FAS, and TNF-α in LE, ME, and HE groups were decreased, and the gene levels of PPARα and CPT-1 were increased (P<0.01 or P<0.05). Conclusion: Swimming with different loads can improve liver functions in AFLD mice, promote lipid droplet degradation, and regulate liver lipid metabolism. The mechanism may be related to the activation of miR-34a/PPARα, and the intervention effect of moderate-load swimming is better.


Assuntos
Fígado Gorduroso Alcoólico , MicroRNAs , Camundongos , Masculino , Animais , Natação , PPAR alfa , Fator de Necrose Tumoral alfa , LDL-Colesterol , Triglicerídeos , RNA Mensageiro
18.
J Ayub Med Coll Abbottabad ; 34(Suppl 1)(3): S707-S710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36414596

RESUMO

Background: Hypoadiponectinemia and raised total leukocyte count have been associated with coronary artery disease. The aim of this study was to investigate association of serum adiponectin levels with total leukocyte count in patients of coronary artery disease belonging to Khyber Pakhtunkhwa. Method: This cross-sectional/analytical study consisted of two groups. Group A contained 100 patients of coronary artery disease while group B contained 100 healthy controls. Consent of the study subjects was obtained, their history was recorded and fasting blood samples were analyzed for serum adiponectin level, total leukocyte count (TLC), serum lipid profile which included serum total cholesterol (T-C), triglyceride level (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Adiponectin level was determined with ELIZA method, TLC was estimated on automated haematology analyzer and lipid profile was determined using enzymatic colorimetric method. SPSS version 21 was used to analyze the data. Results: Subjects with coronary artery disease when compared to healthy subjects showed significantly high level of total leukocyte count (9.26±1.488 vs. 6.37±4.052) and low level of serum adiponectin (4.3±0.80 vs. 9.6±3.69). Moreover, serum lipid profile showed low HDL-C (30.04±9.1 vs. 43.64±7.3) and rose triglyceride (220.1±67.7 vs. 181.86±41.4), total cholesterol (229.3±37.01 vs. 189.4±32.7), and LDL-C (153.78±38.53 vs. 109.16±33.91) levels. Significant negative association of adiponectin with TLC (r -0.826 with p<0.01) was observed in the study subjects. Conclusion: We observed elevated level of total leukocyte count and reduced level of adiponectin in subjects with coronary artery disease. Moreover, hypoadiponectinemia correlated negatively with TLC levels.


Assuntos
Adiponectina , Doença da Artéria Coronariana , Humanos , LDL-Colesterol , Estudos Transversais , Triglicerídeos , Contagem de Leucócitos
19.
Biomed Pharmacother ; 156: 113957, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36411665

RESUMO

annually in Europe, 4 million people die from cardiovascular diseases, the main cause of which is atherosclerosis. In order to slow down the development of atherosclerotic plaques, the main therapeutic goal is to lower LDL cholesterol (LDL-C) level. Undoubtedly, statins are the basis of lipid-lowering therapy for many years. However, a European study shows that only 43% of statin-taking patients achieved their LDL-C targets. PCSK9 inhibitors are a new group of lipid-lowering drugs whose main point of action is the protein discovered in 2003 - the PCSK9 (proprotein convertase subtilisin/kexin 9). This protein is responsible for reducing the density of LDL receptors on the surface of hepatocytes, which increases the value of LDL-C. The discovery of this protein was soon after the basis for the start of research, thanks to which three monoclonal antibodies against PCSK9 were developed - evolocumab, alirocumab, bococizumab - and inclisiran, an inhibitor of PCSK9 synthesis in the liver. In addition to the mechanism of action of PCSK9 inhibitors, resulting in lowering LDL-C level, a number of pleiotropic mechanisms have also been identified, including effects on metabolic processes and inflammation. Until the registration and introduction of above-mentioned drugs into everyday clinical practice, many studies were carried out, in which, in addition to assessing the effectiveness of treatment, the safety and tolerability of the drug were also examined. The purpose of this review is to summarize information on the safety profile of PCSK9 inhibitors, which may help in making therapeutic decision.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Inibidores de PCSK9 , Humanos , Pró-Proteína Convertase 9 , LDL-Colesterol/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
20.
BMC Endocr Disord ; 22(1): 288, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36404325

RESUMO

INTRODUCTION: The importance of genetic and dietary factors in occurrence and progression of chronic diseases such as metabolic syndrome (MetS) has been established. However, complex interrelationships, including direct and indirect effects of these variables are yet to be clarified. So, our aim was to investigate the mediating role of glycemic indices in the relationship between CARTPT rs2239670 polymorphism, socio-demographic and psychological factors and metabolic risk factors and the presence of MetS in adults with obesity. METHODS: In a cross-sectional study of 288 apparently healthy adults with obesity aged 20-50 years, dietary glycemic index (GI) and glycemic load (GL) were measured using a validated semi-quantitative food frequency questionnaire (FFQ). Biochemical parameters, blood pressure and anthropometric indicators were assayed by standard methods. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Structural equation modeling (SEM) was used in the statistical analysis. RESULTS: CARTPT rs2239670 had a positive direct effect on MetS (B = 0.037 ± 0.022; P = 0.043) and, on the other hand, this variant was found to be indirectly associated with MetS presence through mediation of GI (B = 0.039 ± 0.017; P = 0.009). CARTPT was a significant predictor of both dietary GI and GL (B = 1.647 ± 0.080 and B = 3.339 ± 0.242, respectively). Additionally, glycemic indicators appeared to mediate the association of age and gender with LDL-C (B = 0.917 ± 0.332; P = 0.006) and HDL (B = 1.047 ± 0.484; P = 0.031), respectively. GI showed a positive relationship with LDL-C (P = 0.024) in men and similar relationships were found between GL and LDL-C (P = 0.050) and cholesterol (P = 0.022) levels in women. CONCLUSION: The SEM findings suggest a hypothesis of the mediating effect of glycemic indices in the relationship between genetic susceptibility to obesity and MetS presence. Our findings need to be confirmed with large prospective studies.


Assuntos
Carga Glicêmica , Síndrome Metabólica , Humanos , Adulto , Masculino , Feminino , Índice Glicêmico/fisiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Síndrome Metabólica/complicações , Estudos Transversais , LDL-Colesterol , Estudos Prospectivos , Obesidade/epidemiologia , Obesidade/genética , Fatores de Risco , Polimorfismo Genético
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