RESUMEN
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.
Asunto(s)
Anticolesterolemiantes , LDL-Colesterol , Hipercolesterolemia , Humanos , LDL-Colesterol/sangre , Anticolesterolemiantes/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/sangre , Medición de Riesgo , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Inhibidores de PCSK9RESUMEN
BACKGROUND: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear. OBJECTIVES: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years. METHODS: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years. RESULTS: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile. CONCLUSIONS: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.
Asunto(s)
Aterosclerosis , LDL-Colesterol , Humanos , Adulto , Masculino , Femenino , Adulto Joven , Adolescente , LDL-Colesterol/sangre , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Valor Predictivo de las Pruebas , Medición de Riesgo/métodos , Factores de Riesgo , HDL-Colesterol/sangreRESUMEN
Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.
Asunto(s)
Biomarcadores , Enfermedad de la Arteria Coronaria , Proteínas de la Membrana , Análisis de la Aleatorización Mendeliana , Proteómica , Humanos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/patología , Ratones , Animales , Proteínas de la Membrana/genética , Proteínas de la Membrana/sangre , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , LDL-Colesterol/sangre , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Estudios de Casos y Controles , Aterosclerosis/sangre , Aterosclerosis/genéticaRESUMEN
Cardiovascular disease (CVD) is the leading cause of mortality globally. Low-density lipoprotein (LDL) plays an important role in CVD pathophysiology. Research has shown the safety and efficacy of keeping LDL at very low levels for CVD prevention. Therefore, experts recommend intense LDL-lowering approaches starting at young ages, promoting the mantras "the lower, the better" and "the earlier, the better." This commentary discusses the challenges regarding applying aggressive LDL-lowering approaches in the general population, including pharmacological efficacy and side effects, the cost-effectiveness of interventions, and patient adherence to treatment regimens.
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Enfermedades Cardiovasculares , LDL-Colesterol , Lipoproteínas LDL , Prevención Primaria , Humanos , Enfermedades Cardiovasculares/prevención & control , Prevención Primaria/métodos , Lipoproteínas LDL/sangre , LDL-Colesterol/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Análisis Costo-BeneficioRESUMEN
BACKGROUND: The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in pre-analytical requirements, methods, nomenclature, and reporting work flows. CONTENT: The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. SUMMARY: Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases.
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Lípidos , Lipoproteínas , Humanos , Lipoproteínas/sangre , Lipoproteínas/análisis , Lípidos/sangre , Lípidos/análisis , LDL-Colesterol/sangre , Apolipoproteínas B/sangre , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Lipoproteína(a)/sangreRESUMEN
AIM: To examine the long-term results and treatment effectiveness of liver transplantation (LT) in the treatment of homozygous familial hypercholesterolemia (HoFH) in children and adolescents. METHOD: Patients who underwent LT due to HoFH between 2007 and 2023 were included in the study. The patients' demographic data, clinical findings, preoperative and postoperative laboratory examinations, transplantation complications, and postoperative disease courses were evaluated. RESULTS: There were five boys with an average age of 6.2 (median: 6, range 4-10) years in the study. The average total cholesterol level of the patients before transplantation was 923 (median: 950, range: 780-1002) mg/dL and the average LDL-cholesterol level was 864 (median: 852, range: 770-957) mg/dL. No patients died of transplant-related complications. After an average follow-up of 9.2 (median: 9, range: 1.5-16) years, the average total cholesterol level of the patients was 197 (median: 164, range: 137-359) mg/dL, and the average LDL-cholesterol level was 138 (median: 92, range: 85-313) mg/dL. Four (80%) patients developed atherosclerotic cardiovascular disease during follow-up, and two (40%) died of this cause. CONCLUSION: LT in the treatment of HoFH did not help our patients reach the target LDL-cholesterol level after transplantation and did not prevent the development of cardiovascular disease. Therefore, LT alone is not curative in the treatment of HoFH.
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LDL-Colesterol , Hiperlipoproteinemia Tipo II , Trasplante de Hígado , Humanos , Masculino , Niño , Hiperlipoproteinemia Tipo II/cirugía , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/terapia , Preescolar , Resultado del Tratamiento , LDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Homocigoto , Adolescente , Estudios Retrospectivos , Colesterol/sangreRESUMEN
OBJECTIVE: The inconsistency in conclusions from early observational studies has sparked our interest in elucidating the relationship between lipid levels and susceptibility to hyperemesis gravidarum (HG). This study wishes to employed Mendelian randomization analysis to investigate the causal relationship between low-density lipoprotein cholesterol (LDL-C) and HG. METHODS: We employed Tow-Sample MR analysis to investigate the causal associations between LDL-C and HG. Specific variables were selected from GWAS database for MR analysis, using single nucleotide polymorphisms (SNPs) as our instruments. The threshold for significant SNPs as genetic instruments has been set at 5 × 10-8. F-statistic was employed to validate the strength of exposure instruments. The causality was mainly evaluated by Inverse Variance Weighted method (IVW). To address potential bias from the selection of genetic variants with pleiotropic effects, sensitivity analysis was performed by Cochrane Q-test, MR Egger, weighted median, MR-PRESSO and Leave-one-out methods. To validate the directionality of causal relationships, we employed Steiger test to filter SNPs. At last, we conducted reverse MR to exclude the causal impact of HG on LDL-C levels. RESULTS: Our MR results identified the effect of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG (OR:1.30; 95%CI:1.03-1.65; p = 0.028). In reverse MR analyses, no evidence was found for causal effect of HG on LDL-C levels (OR:1.00; 95%CI:1.00-1.01; p = 0.163). Sensitivity analyses were used to confirm reliability. CONCLUSION: This study may have provided evidence of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG. Appropriate lowering LDL-C levels may serve as a preventive and treatment measure for HG.
Asunto(s)
LDL-Colesterol , Hiperemesis Gravídica , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Embarazo , LDL-Colesterol/sangre , Hiperemesis Gravídica/genética , Hiperemesis Gravídica/sangre , Hiperemesis Gravídica/epidemiología , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Factores de RiesgoRESUMEN
AIMS: The purpose of this study was to analyze the dynamic trends of ischemic heart disease (IHD) mortality attributable to high low-density lipoprotein cholesterol (LDL-C). METHODS: Data on IHD mortality attributable to high LDL-C from 1990 to 2021 were extracted from the global disease burden database. Joinpoint software was used to estimate the average annual percentage change (AAPC) in the age-standardized mortality rate (ASMR). An ageâperiodâcohort model was used to analyze the impacts of age, period, and cohort on these changes. The Bayesian framework was used to predict IHD mortality attributable to high LDL-C from 2022 to 2040. RESULTS: The overall ASMR of IHD attributable to high LDL-C decreased from 50. 479 per 100,000 people in 1990 to 32.286 per 100,000 people in 2021, and ASMR of IHD attributable to high LDL-C was higher in males than in females. The longitudinal age curves of the overall IHD mortality attributable to high LDL-C showed a monotonic upward trend, especially after 65 years of age. The period and cohort effect relative risk (RR) values of overall IHD mortality attributable to high LDL-C showed a downward trend. The overall ASMR of IHD attributable to high LDL-C is predicted to show a downward trend, and male IHD mortality attributable to high LDL-C is expected to be higher than that of females. CONCLUSION: This study revealed a sustained decrease in IHD mortality attributable to high LDL-C over three decades, with a continued decline expected. Despite this, gender disparities persist, with males experiencing higher mortality rates and elderly individuals remaining a vulnerable group.
Asunto(s)
LDL-Colesterol , Isquemia Miocárdica , Humanos , Isquemia Miocárdica/mortalidad , Isquemia Miocárdica/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , LDL-Colesterol/sangre , Adulto , Estudios de Cohortes , Teorema de Bayes , Factores de Edad , Anciano de 80 o más Años , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVE: The value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) assessment in the context of metabolic abnormalities is growing in importance. Nevertheless, the relationship between NHHR and hyperuricemia (HUA) is unknown. This study seeks to investigate the relationship between NHHR and HUA. METHODS: The data derived from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) included 7,876 adult participants. The multivariable logistic regression model, subgroup analysis and smooth fitting curve were utilized in order to investigate the association between NHHR and HUA. RESULTS: In the fully adjusted model 3, NHHR was significantly associated with HUA. Specifically, participants in the highest quartile of NHHR had 1.95 times higher odds of HUA prevalence compared to those in the lowest quartile [2.95 (2.39, 3.64), P < 0.0001]. Although the overall trend suggested a positive association, further analysis using smooth fitting curves and threshold effect analysis indicated that this association was nonlinear, with an inflection point at 5.8. The positive association persisted across different HUA definitions and after removing outliers. Subgroup analysis showed significant interactions between NHHR and HUA in different races and diabetes statuses. The odds of HUA prevalence were higher among non-diabetic participants [1.40 (1.32, 1.49), P < 0.0001] compared to diabetic participants [1.18 (1.06, 1.32), P = 0.0031]. Mexican Americans had the lowest odds of HUA prevalence [1.09 (0.92, 1.27), P = 0.2413] compared to other races. CONCLUSIONS: There is a significant positive association between NHHR and HUA, indicating that NHHR may serve as a potential risk assessment maker for HUA, although further prospective studies are needed for validation.
Asunto(s)
HDL-Colesterol , Hiperuricemia , Encuestas Nutricionales , Humanos , Hiperuricemia/sangre , Hiperuricemia/epidemiología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , HDL-Colesterol/sangre , Adulto , Prevalencia , Factores de Riesgo , Modelos Logísticos , Anciano , Colesterol/sangre , LDL-Colesterol/sangreRESUMEN
BACKGROUND: The effect of proprotein convertase subtilisin kexin type (PCSK9) inhibitors on blood lipids and major adverse cardiovascular events (MACEs) is still controversial for acute coronary syndrome (ACS) patients. This study aimed to evaluate the efficacy and safety of PCSK9 inhibitors for ACS patients. METHODS: We searched the following databases until March 2023: PubMed, Embase, Cochrane, Web of Science, CNKI, Chongqing VIP Database and Wan Fang Database. Finally, all randomized controlled trials, retrospective studies and prospective studies were included in the analysis. RESULTS: A total of 20 studies involving 48,621 patients were included in this meta-analysis. The results demonstrated that PCSK9 inhibitors group was more beneficial for ACS patients compared to control group (receiving statins alone or placebo). The meta-analysis showed: there was no significant difference in high density lipoprotein cholesterol between PCSK9 inhibitors group and control group (standard mean differenceâ =â 0.17, 95% confidence interval [CI]: -0.02 to 0.36, Pâ =â .08), while the level of low density lipoprotein cholesterol in PCSK9 inhibitors group was lower than that in control group (standard mean differenceâ =â -2.32, 95% CI: -2.81 to -1.83, Pâ <â .00001). Compared with the control group, the PCSK9 inhibitors group also decreased the levels of total cholesterol and triglycerides (mean differenceâ =â -1.24, 95% CI: -1.40 to -1.09, Pâ <â .00001, mean differenceâ =â -0.36, 95% CI: -0.56 to -0.16, Pâ =â .0004). Moreover, compared with the control group, PCSK9 inhibitors group could reduce the incidence of MACEs (relative risk [RR]â =â 0.87, 95% CI: 0.83-0.91; Pâ <â .00001). However, this study showed that the incidence of drug-induced adverse events in PCSK9 inhibitors group was higher than that in the control group (RRâ =â 1.15, 95% CI: 1.05-1.25, Pâ <â .0001). CONCLUSION: Although this study demonstrates that PCSK9 inhibitors have higher drug-induced adverse events, they can not only reduce low-density lipoprotein cholesterol levels but also reduce the incidence of MACEs simultaneously. However, these findings needed to be further verified through large sample, multicenter, double-blind randomized controlled trials.
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Síndrome Coronario Agudo , Inhibidores de PCSK9 , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/sangre , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Anticolesterolemiantes/uso terapéutico , Anticolesterolemiantes/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Proproteína Convertasa 9RESUMEN
Probiotics have shown potential in managing hypercholesterolemia and related metabolic conditions. This study evaluated the effects of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 on the gut microbiome and metabolic health in patients with hypercholesterolemia, and was registered in the Thai Clinical Trial Registry (TCTR 20220917002). In a randomized, double-blind, placebo-controlled trial, 22 hypercholesterolemic participants received either the probiotic or a placebo daily for 90 days. Fecal samples collected before and after the intervention revealed significant microbiome changes, including a decrease in Subdoligranulum, linked to rheumatoid arthritis, and an increase in Flavonifractor, known for its anti-inflammatory properties. Additionally, the probiotic group exhibited a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels. These findings suggest that L. paracasei TISTR 2593 can modulate the gut microbiome and improve metabolic health, warranting further investigation into its mechanisms and long-term benefits.
Asunto(s)
LDL-Colesterol , Heces , Microbioma Gastrointestinal , Hipercolesterolemia , Probióticos , Humanos , Probióticos/administración & dosificación , Probióticos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Hipercolesterolemia/terapia , Hipercolesterolemia/sangre , Masculino , Femenino , Método Doble Ciego , Persona de Mediana Edad , Heces/microbiología , LDL-Colesterol/sangre , Lacticaseibacillus paracasei , Adulto , Suplementos Dietéticos , AncianoRESUMEN
The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains other bioactive compounds such as γ-oryzanol (OZ) and γ-aminobutyric acid (GABA). In a randomized, placebo-controlled, double-blind trial, the efficacy and tolerability of a food supplement (FS) based on an ingredient standardized to contain monacolins (4.5%), OZ, and GABA were evaluated in subjects with mild dyslipidemia. For the duration of the trial, enrolled subjects (n = 44, each group) received the FS or placebo and were instructed to use an isocaloric diet. Compared to the placebo group, after a 3 months of the FS, the mean low-density lipoprotein cholesterol and mean TC values were reduced by 19.3 and 8.3%, respectively, while the mean high-density lipoprotein cholesterol value increased by 29.3%. On average, the subjects shifted from very high to moderate CVD risk. Glucose metabolism and hepatic and renal parameters did not change after the treatment and no adverse events were reported. Guidelines to handle hypercholesterolemia with food supplements in specific clinical settings are needed to better manage mild dyslipidemia.
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Suplementos Dietéticos , Dislipidemias , Fenilpropionatos , Ácido gamma-Aminobutírico , Humanos , Método Doble Ciego , Masculino , Femenino , Persona de Mediana Edad , Dislipidemias/tratamiento farmacológico , Dislipidemias/sangre , Fenilpropionatos/uso terapéutico , Adulto , Lovastatina/uso terapéutico , LDL-Colesterol/sangre , Resultado del Tratamiento , HDL-Colesterol/sangreRESUMEN
This study was a meta-analysis of patient data to investigate the therapeutic effects of inclisiran on LDL-C, PCSK9, and TC in patients with atherosclerosis. Authors searched the Cochrane Library, Pubmed, EMBASE, and Web of Science databases for randomised controlled trials. Data of 4,731 subjects from five randomised clinical trials were included in this analysis. Patients treated with the PCSK9 inhibitor inclisiran had significantly lower LDL-C levels than those treated with placebo or a statin (mean difference (MD) -1.477; 95% CI -1.551 to -1.403; p <0.001; I2 = 7.2%). The average level of PCSK9 was also relatively lower ((MD) -2.579; 95% CI -2.694 to -2.464; p <0.001; I2 = 36%). They exhibited significant reductions in total cholesterol protein levels ((MD) -1.477; 95% CI -1.585 to -1.369; p <0.001; I2 = 46.7%). Inclisiran reduced LDL-C and PCSK9 levels as well as TC and Apo B levels significantly in patients with atherosclerotic cardiovascular disease (ASCVD). Key Words: Inclisiran, Low-density lipoprotein cholesterol, Atherosclerosis, Adverse events, Meta-analysis.
Asunto(s)
Enfermedades Cardiovasculares , LDL-Colesterol , Inhibidores de PCSK9 , Humanos , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Aterosclerosis/prevención & control , Proproteína Convertasa 9 , Ensayos Clínicos Controlados Aleatorios como Asunto , ARN Interferente PequeñoRESUMEN
We examined the association between walkability and blood lipids in a nationally representative sample of 29,649 participants aged 3-79 years who participated in the Canadian Health Measures Survey (CHMS) cycles 1 to 6. We focused on seven lipid biomarkers: apolipoprotein A (Apo A), apolipoprotein B (Apo B), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and TC/HDL. Cross-sectional associations were analyzed using generalized linear mixed models incorporating survey-specific sampling weights. An increase in the Canadian Active Living Environments Index, a measure of neighborhood walkability, equivalent to the magnitude of its interquartile range (IQR) was associated with the following percentage (95% confidence intervals (CI)) changes in lipids: decreased TG, -2.85 (-4.77, -0.93) and TC/HDL, -1.68 (-2.80, -0.56), and increased HDL, 1.68 (0.93, 2.42). Significant effects were largely restricted to adults (aged 17 to 79). In the younger age group there were no significant associations between walkability and lipids in the fully adjusted model. Significant associations were more frequently seen in females than males. For females, fully adjusted significant inverse associations were observed for TG, LDL, and TC/HDL, and there were positive associations with HDL and Apo A. Canadians living in more walkable neighborhoods have more favorable lipid profiles, suggesting that the built environment has the potential to influence the risk profile for cardiovascular health, especially among adults and females.
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Características de la Residencia , Triglicéridos , Caminata , Humanos , Persona de Mediana Edad , Masculino , Femenino , Adulto , Anciano , Canadá/epidemiología , Adolescente , Triglicéridos/sangre , Niño , Estudios Transversales , Adulto Joven , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Preescolar , Apolipoproteínas B/sangre , Lípidos/sangre , Apolipoproteínas A/sangre , Biomarcadores/sangreRESUMEN
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have represented an important change in the management of hypercholesterolemia, although, until now, they have barely been used. Without PCSK9i, many patients with atherosclerotic cardiovascular disease (CVD) or those at very high risk do not reach their therapeutic LDLc objectives. OBJECTIVE: The analysis aimed to examine the clinical and biochemical characteristics of subjects receiving PCSK9i treatment in the Dyslipidemia Registry of the Spanish Atherosclerosis Society. METHODS: All consecutive subjects aged ≥ 18 years from different Lipid Units included in the Dyslipidemia Registry of the SEA were analyzed. Inclusion criteria consisted of unrelated patients aged ≥ 18 at the time of inclusion with hypercholesterolemia (LDL-C ≥ 130 mg/dL or non-HDL-C ≥ 160 mg/dL after the exclusion of secondary causes) who were studied for at least two years after inclusion. Participants' baseline and final visit clinical and biochemical characteristics were analyzed based on whether they were on primary or secondary prevention and whether they were taking PCSK9i at the end of follow-up. RESULTS: Eight hundred twenty-nine patients were analyzed, 7014 patients in primary prevention and 1281 in secondary prevention at baseline. 4127 subjects completed the required follow-up for the final analysis. The median follow-up duration was 7 years (IQR 3.0-10.0). Five hundred patients (12.1%) were taking PCSK9i at the end of the follow-up. The percentage of PCSK9i use reached 35.6% (n = 201) and 8.7% (n = 318) in subjects with and without CVD, respectively. Subjects on PCSK9i and oral lipid-lowering agents with and without CVD achieved LDLc reductions of 80.3% and 75.1%, respectively, concerning concentrations without lipid-lowering drugs. Factors associated with PCSK9i use included increasing age, LDLc without lipid-lowering drugs and the Dutch Lipid Clinic Network (DLCN) score. However, hypertension, diabetes, smoking, and LDLc after oral lipid-lowering drugs were not independent factors associated with PCSK9i prescription. In subjects with CVD, the use of PCSK9i was higher in men than in women (an odds ratio of 1.613, P = 0.048). CONCLUSIONS: Approximately one-third of CVD patients received PCSK9i at the end of follow-up. The use of PCSK9i was more focused on baseline LDLc concentrations rather than on CVD risk. Women received less PCSK9i in secondary prevention compared to men.
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Enfermedades Cardiovasculares , LDL-Colesterol , Inhibidores de PCSK9 , Prevención Secundaria , Humanos , Inhibidores de PCSK9/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Prevención Secundaria/métodos , Anciano , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , LDL-Colesterol/sangre , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/sangre , Prevención Primaria/métodos , Anticolesterolemiantes/uso terapéutico , Sistema de Registros , Proproteína Convertasa 9/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
HMG-CoA reductase inhibitors (statins) were discovered in the early 1970s in Japan and were originally used to treat patients with hereditary hyperlipidemia. In the late 1990s and early 2000s, clinical trials using statins for primary and secondary prevention showed the possibility of reducing cardiovascular (CV) and, in some cases, all-cause mortality. Intensive statin therapy (atorvastatin 80 mg/day and rosuvastatin 40 mg/day) compared to initial doses provides an additional 16% reduction in CV complications. Regression studies with the original rosuvastatin using intracoronary ultrasound and other modern methods have shown the possibility of stabilization and regression of atherosclerosis in the carotid and coronary arteries. High-dose statin therapy is generally well tolerated; the incidence of clinically significant adverse liver reactions does not exceed 2-3 per 100,000 people, and the incidence of myopathies with increased creatine kinase over 10 upper limits of normal is not higher than 1 per 10,000 people per year. Long-term statin treatment does not increase the risk of dementia and, in some studies, reduced the risk of Alzheimer's disease. Achieving target levels of low-density lipoprotein cholesterol (LDL-C) in routine practice does not exceed 5-11%; one of the main reasons for that is the rare (2-3%) prescription of high doses of statins. Increasing statin doses in routine clinical practice will optimize the treatment of patients with high CV risk and will contribute to further reduction of mortality in our country.
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Enfermedades Cardiovasculares , Relación Dosis-Respuesta a Droga , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangreRESUMEN
BACKGROUND: Young adults with elevated LDL-C may experience increased burden of additional cardiovascular disease (CVD) risk factors. It is unclear how much LDL-C levels, a modifiable factor, correlate with non-LDL-C CVD risk factors among young adults or how strongly these CVD risk factors are associated with long-term predicted CVD risk. We quantified clustering of non-LDL-C CVD risk factors by LDL-C among young adults to assess the association between non-LDL-C and LDL-C risk factors with predicted CVD risk in young adults. METHODS: The current analysis is a cross-sectional study of adults < 40 years with an LDL-C< 190 mg/dL participating in the National Health and Nutrition Examination Survey (NHANES) between January 2015 and March 2020. We measured the prevalence of non-LDL-C risk factors by LDL-C and association between LDL-C and non-LDL-C risk factors with predicted risk of CVD by the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations. RESULTS: Among 2108 young adults, the prevalence of LDL-C ≥ 130 mg/dL was 15.5%. Compared with young adults with LDL-C < 100 mg/dL, those with LDL-C 100-< 130, 130-< 160, and 160-< 190 mg/dL had greater non-LDL-C risk factors. Both LDL-C and non-LDL-C risk factors were independently associated with a 30-year risk of CVD (OR 1.05, 95% CI 1.03-1.07 and OR 1.17, 95% CI 1.12-1.23, respectively). The association of LDL-C and 30-year risk did not vary by non-LDL-C risk factor burden (pinteraction = 0.43). CONCLUSION: Non-LDL-C risk factors cluster among increasing levels of LDL-C in young adults. Greater guidance on how to manage cardiovascular risk factors in young adults is needed.
Asunto(s)
Enfermedades Cardiovasculares , LDL-Colesterol , Factores de Riesgo de Enfermedad Cardiaca , Encuestas Nutricionales , Humanos , Masculino , Estudios Transversales , Femenino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , LDL-Colesterol/sangre , Adulto , Medición de Riesgo/métodos , Estados Unidos/epidemiología , Adulto Joven , Prevalencia , Biomarcadores/sangre , Factores de RiesgoRESUMEN
BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. METHODS: In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch's tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman's correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. RESULTS: It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from - 0.228 to -0.385. Further regression analysis presented ß values between - 0.954 and - 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. CONCLUSIONS: The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. TRIAL REGISTRATION: NCT05644548, December 1, 2022.
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LDL-Colesterol , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Masculino , Femenino , Vasos Retinianos/diagnóstico por imagen , LDL-Colesterol/sangre , Anciano , Estudios Transversales , Persona de Mediana Edad , Anciano de 80 o más Años , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/irrigación sanguínea , Factores de RiesgoRESUMEN
BACKGROUND: Lipid levels have been suggset to be correlated with multiple myeloma (MM) risk, though causality remains unconfirmed. To explore this further, a detailed study combining meta-analysis and Mendelian randomization (MR) was conducted. METHODS: Literature searches were performed on PubMed and Embase; summary data for plasma lipid traits were extracted from the IEU and MM data from the FinnGen database. Meta-analysis and MR were utilized to analyze the link of lipids with MM risk, including mediator MR to identify potential mediators. The study was conducted in accordance with PRISMA and STROBE-MR guidelines. RESULTS: Observational studies analyzed through meta-analysis showed that elevated levels of LDL, HDL, total cholesterol (TC), and triglycerides correlate with a lower risk of MM, with HRs of 0.73, 0.59, 0.60, and 0.84, respectively. MR analysis confirmed a potential causal link of triglyceride with a reduced MM risk (OR: 0.67, 95% CI: 0.46-0.98), independent of BMI. Mediation analysis pointed to X-11,423-O-sulfo-L-tyrosine and neuropilin-2 as potential mediators. CONCLUSIONS: The findings suggest that higher lipid levels (LDL, HDL, TC, and triglycerides) are linked with a reduced MM risk, and higher triglyceride levels are causally associated with a reduced MM risk. This suggests new avenues for therapeutic interventions targeting MM.
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Análisis de la Aleatorización Mendeliana , Mieloma Múltiple , Triglicéridos , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/sangre , Triglicéridos/sangre , Factores de Riesgo , LDL-Colesterol/sangre , HDL-Colesterol/sangre , Colesterol/sangre , Lípidos/sangreRESUMEN
BACKGROUND: Point-of-care testing (POCT) is commonly used in epidemiological surveys due to its various advantages, such as portability and immediate test results. The CardioChek® PA analyser 3-in-1 lipid panel measures total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. This study tested the reliability and diagnostic accuracy of the CardioChek® PA analyser using a 3-in-1 lipid panel. METHODS: A cross-sectional study design with quota sampling was used. A total of 203 respondents aged 18 years and above from a research centre in the Ministry of Health, Malaysia, were recruited. Venous blood was sent to the laboratory and tested with Siemens Atellica CH, while a POCT analyser was used for capillary blood measurements. Intraclass coefficient correlation (ICC) analysis was employed to determine the agreement between capillary and venous blood parameters. The diagnostic performance of the evaluated tests was evaluated using STATA version 12. RESULTS: The agreement between capillary and laboratory venous blood was moderate (0.64-0.67) for TC and HDL, good (0.75) for LDL and excellent (0.91) for TG). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were as follows: TC, 57.1%, 94.3%, 92.3% and 64.8%; TG, 76.0%, 100%, 100%, and 96.6%; HDL, 96.2%, 83.2%, 47.2% and 99.3%; and LDL, 81.0%, 100%, 100% and 68.3%, respectively. CONCLUSIONS: The CardioChek® PA analyser showed acceptable diagnostic accuracy for screening high-risk individuals more often in places where laboratories are inaccessible. It could also be used in clinical settings where patients would benefit from swift treatment decisions.