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1.
Int J Cardiol ; 402: 131857, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38360103

ABSTRACT

BACKGROUND AND AIMS: Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event. METHODS: Danish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured. RESULTS: A total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated. CONCLUSIONS: Many Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.


Subject(s)
Anticholesteremic Agents , Atherosclerosis , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypercholesterolemia , Humans , Hypercholesterolemia/diagnosis , Hypercholesterolemia/drug therapy , Hypercholesterolemia/epidemiology , Cholesterol, LDL , Cohort Studies , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Atherosclerosis/diagnosis , Atherosclerosis/drug therapy , Atherosclerosis/epidemiology , Denmark/epidemiology , Anticholesteremic Agents/therapeutic use
2.
Atherosclerosis ; 384: 117148, 2023 11.
Article in English | MEDLINE | ID: mdl-37302923

ABSTRACT

BACKGROUND AND AIMS: Cardiovascular (CV) diseases show clear differences in clinical manifestation and treatment outcomes between men and women. To reduce sex disparities in achieving lipid-lowering therapy (LLT) goals, a sex-focused assessment is essential and more studies are needed to bring new evidence to clinicians. This study aims to assess the role of sex in attaining low-density lipoprotein cholesterol (LDL-C) goals, after correction for age, CV risk category, LLT intensity, and presence of mental health disorder and social deprivation. METHODS: A retrospective cohort analysis of patients aged 40-85, followed in 1 hospital and 14 primary care centers in Portugal, using electronic health records from 1/1/2012 to 31/12/2020, was performed. The analysis considered an episode-based design, where exposure consists of any time when LLT was started or intensity changed. The likelihood of reaching the LDL-C goal according to contemporary ESC/EAS guidelines was modeled using multivariate Cox regression. LDL-C goal achievement at 180 days was defined as the outcome. The analysis was repeated at 30-day follow-up intervals up to 360 days, and also stratified by CV risk category. RESULTS: We identified 40,032 exposure episodes (LLT initiation or intensity change) in 30,323 distinct patients. Male sex, older age, lower CV risk and increasing LLT intensity were associated with improved LDL-C control. Women were 22% less likely to reach the LDL-C goal than men (HR = 0.78, 95% CI:0.73, 0.82) independently of covariates. CONCLUSIONS: Women have a lower likelihood of attaining LDL-C goals than men after adjustment for LLT intensity, age, CV risk category, presence of mental health disorder and social deprivation. This finding underscores the need for further investigation and tailoring of LLT management strategies in women.


Subject(s)
Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Male , Female , Cholesterol, LDL , Retrospective Studies , Sex Characteristics , Cohort Studies , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Primary Health Care , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
3.
Clin Epidemiol ; 15: 435-446, 2023.
Article in English | MEDLINE | ID: mdl-37033124

ABSTRACT

Purpose: Statins reportedly increase the survival of patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis), but this association might be confounded by socioeconomic status. We examined the prevalence of statin use and socioeconomic and demographic predictors of statin initiation and discontinuation among patients with ALD cirrhosis. Patients and Methods: Using Danish nationwide healthcare registries, we examined statin use among patients diagnosed with ALD cirrhosis in 1997-2018. We computed the prevalence of statin use and incidence of statin initiation and discontinuation, and we used multivariable Cox regression to identify predictors of statin initiation and discontinuation. Results: We identified 28,260 patients with ALD cirrhosis in 1997-2018. During this period, the prevalence of statin use rose sharply, reaching 19.0% in late 2018. Among patients diagnosed with ALD cirrhosis after 2010, 16.9% were using statins when they were diagnosed with cirrhosis. Among the patients who did not use statins initially, those with lower educational attainment were more likely to begin taking them than those with higher attainment. Also, cohabiting patients were more likely to begin than patients who lived alone, and employed patients were more likely to begin compared to patients outside the labour force. Among current statin users, unemployment predicted statin discontinuation. Conclusion: The use of statins has become increasingly prevalent among Danish patients with ALD cirrhosis, reaching 19.0% in 2018. Employment, cohabitation, and a short education predicted statin initiation after ALD cirrhosis diagnosis, and unemployment predicted statin discontinuation. Overall, statin use was not a marker of a high socioeconomic status.

4.
Front Immunol ; 13: 1057546, 2022.
Article in English | MEDLINE | ID: mdl-36479100

ABSTRACT

Based on the structural and signaling roles of cholesterol, which are necessary for immune cell activity, high concentrations of cholesterol and its metabolites not only trigger malignant cell activities but also impede immune responses against cancer cells. To proliferate and evade immune responses, tumor cells overcome environmental restrictions by changing their metabolic and signaling pathways. Overexpression of mevalonate pathway enzymes and low-density lipoprotein receptor cause elevated cholesterol synthesis and uptake, respectively. Accordingly, cholesterol can be considered as both a cause and an effect of cancer. Variations in the effects of blood cholesterol levels on the outcome of different types of cancer may depend on the stage of cancer. However, positive effects of cholesterol-lowering drugs have been reported in the treatment of patients with some malignancies.


Subject(s)
Cholesterol , Neoplasms , Humans
6.
Braz. J. Pharm. Sci. (Online) ; 58: e20400, 2022. tab
Article in English | LILACS | ID: biblio-1403737

ABSTRACT

Abstract Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. Dyslipidemia treatment can reduce the number of deaths caused by CVD, by decreasing the lipid profile. Evaluate the pharmacotherapeutic follow-up effectiveness in patients with dyslipidemia, regarding clinical and laboratory aspects. A quasi-experimental trial was performed in 12 months. The studied population was included patients with dyslipidemia who received a pharmacotherapeutic follow-up, which was evaluated according to the Pharmacotherapy Workup developed by the Brazilian Ministry of Health. Clinical and laboratory evaluations were performed at the baseline, after a 6 and 12-months period. The statistical analyzes were performed with the normality test of Lilliefors, Cramer Von Misses, and Anderson Darling, later the t-paired test. This study demonstrated that after 6-months of intervention, statistically significant results were verified in the reduction of LDL-cholesterol, total cholesterol, increase in HDL-cholesterol, and reduction in the blood pressure. It was observed that for high-risk patients, the achievement of targets in the lipid profile and HbA1C occurred only after 12-months, because, this population needs more aggressive targets and expressive interventions. Pharmacotherapeutic follow-up in patients with dyslipidemia reduced lipid blood levels and promoted positive clinical and laboratory outcomes.


Subject(s)
Patients/classification , Unified Health System , Delivery of Health Care , Drug Therapy , Dyslipidemias/diagnosis , Health Services Needs and Demand
7.
Ann Intern Med ; 174(4): JC38, 2021 04.
Article in English | MEDLINE | ID: mdl-33819068

ABSTRACT

SOURCE CITATION: Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396:1637-43. 33186535.


Subject(s)
Anticholesteremic Agents , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Anticholesteremic Agents/adverse effects , Cardiovascular Diseases/prevention & control , Cholesterol, LDL , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Treatment Outcome
8.
Biomed Pharmacother ; 133: 110969, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33166762

ABSTRACT

Constituents of lupin seeds, like γ-conglutin and lupanine, have gained attention as potential complementary treatments for dysglycaemia management. Notwithstanding, the effect of other lupin components on carbohydrate metabolism, including ß-conglutin protein, has received little attention. Here, we investigated the influence of the acute and chronic administration of ß-conglutin on glycaemia modulation in normal and streptozotocin induced-to-diabetes rats. We analysed the liver transcriptome modulation exerted by ß-conglutin in diabetes-induced rats using DNA microarrays to scout for potential molecular targets and pathways involved in this biological response. The acute administration of ß-conglutin reduced the incremental area under the curve of glycaemia in normal and diabetes-induced animals. In a seven-day study with diabetic animals, glycaemia increased significantly in non-treated animals but remained unchanged in animals treated with a daily dose of ß-conglutin. Total cholesterol was significantly lower at the end of the experimental period (-21.8 %, p = 0.039). The microarray and gene ontology analyses revealed several targets and pathways potentially modulated by ß-conglutin treatment, including a possible down-regulation of Jun kinase activity. Moreover, our data indicate that targets related to oxidative stress, inflammation, and estrogenic activity might orchestrate these metabolic effects. In conclusion, our findings show that ß-conglutin may help manage postprandial glycaemia and reduce cholesterol levels under the dysglycaemia stage. We identified and proposed new potential molecular targets for further research related to the mechanism of action of ß-conglutin.


Subject(s)
Anticholesteremic Agents/pharmacology , Blood Glucose/drug effects , Cholesterol/blood , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Liver/drug effects , Lupinus , Plant Extracts/pharmacology , Plant Proteins/pharmacology , Seed Storage Proteins/pharmacology , Transcriptome/drug effects , Animals , Anticholesteremic Agents/isolation & purification , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , Gene Regulatory Networks , Hypoglycemic Agents/isolation & purification , Liver/metabolism , Lupinus/chemistry , Male , Plant Extracts/isolation & purification , Plant Proteins/isolation & purification , Rats, Wistar , Streptozocin
9.
Endocrinol Metab (Seoul) ; 35(2): 298-307, 2020 06.
Article in English | MEDLINE | ID: mdl-32615714

ABSTRACT

BACKGROUND: A growing number of functional foods have been proposed to reduce cholesterol levels and the Portfolio Diet, which includes a combination of plant sterols, fibres, nuts, and soy protein, reduces low density lipoprotein cholesterol (LDL-C) from 20% to 30% in individuals with hyperlipidaemia. In this pilot study, the aim was to investigate whether a Mediterranean Diet incorporating a new and simple combination of cholesterol-lowering foods, excluding soy and nuts (namely the Portfolio-Mediterranean Diet), would reduce LDL-C levels, in the short-term, better than a Mediterranean Diet plus a sterol-enriched yogurt or a Mediterranean Diet alone. METHODS: We retrospectively evaluated 24 individuals on a Portfolio-Mediterranean Diet and 48 matched individuals on a Mediterranean Diet with or without a sterol-enriched yogurt (24 each groups) as controls. RESULTS: At follow-up (after 48±12 days), we observed an LDL reduction of 21±4, 23±4, and 44±4 mg/dL in the Mediterranean Diet alone, Mediterranean Diet plus yogurt and Portfolio-Mediterranean Diet respectively (P<0.001). CONCLUSION: A Portfolio-Mediterranean Diet, incorporating a new combination of functional foods such as oats or barley, plant sterols, chitosan, and green tea but not soy and nuts, may reduce LDL of 25% in the short term in individuals with hypercholesterolemia.


Subject(s)
Diet, Mediterranean/statistics & numerical data , Hypercholesterolemia/diet therapy , Sterols/metabolism , Yogurt/statistics & numerical data , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
10.
J Am Coll Cardiol ; 74(20): 2496-2507, 2019 11 19.
Article in English | MEDLINE | ID: mdl-31727288

ABSTRACT

BACKGROUND: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline includes recommendations for intensive lipid-lowering therapy in patients at very high risk for atherosclerotic cardiovascular disease (ASCVD) events. OBJECTIVES: This study sought to estimate event rates among adults with a history of ASCVD who met and did not meet the definition of very high risk in the 2018 AHA/ACC cholesterol guideline. METHODS: Data from U.S. adults with health insurance in the MarketScan database who had a history of ASCVD on January 1, 2016 (n = 27,775) were analyzed. Very high risk for ASCVD events was defined as a history of ≥2 major ASCVD events or 1 event and ≥2 high-risk conditions. Patients were followed through December 31, 2017, for ASCVD events, including myocardial infarction, ischemic stroke, and major adverse limb events. RESULTS: Overall, 15,366 patients (55.3%) with ASCVD met the definition of very high risk. Among patients with and without very high risk, the ASCVD event rate per 1,000 person-years was 53.1 (95% confidence interval [CI]: 50.1 to 56.1) and 17.0 (95% CI: 15.2 to 18.9), respectively. Among patients with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions, the ASCVD event rate per 1,000 person-years was 89.8 (95% CI: 82.2 to 98.0) and 41.3 (95% CI: 38.3 to 44.4), respectively. The age- and sex-adjusted hazard ratios for ASCVD events among patients with very high risk, overall, with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions versus those without very high risk were 2.98 (95% CI: 2.63 to 3.37), 4.89 (95% CI: 4.22 to 5.66), and 2.33 (95% CI: 2.04 to 2.66), respectively. CONCLUSIONS: The 2018 AHA/ACC cholesterol guideline directs intensive lipid-lowering therapy to adults with a very high ASCVD event rate.


Subject(s)
Anticholesteremic Agents/therapeutic use , Atherosclerosis/complications , Myocardial Ischemia/epidemiology , Adult , Aged , Aged, 80 and over , Atherosclerosis/drug therapy , Female , Humans , Male , Middle Aged , Patient Selection , Practice Guidelines as Topic , Retrospective Studies , Risk Factors , United States
12.
Regul Toxicol Pharmacol ; 109: 104509, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31669197

ABSTRACT

The basis of the association between statin use and cataract has been explored using the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) through January 2019. The reporting odds ratios (RORs) as a measure of disproportionality for reported cataracts and individual statins have been calculated. Subgroup analyses according statin lipophilicity, sex, and age groups have been performed. Moreover, RORs have been calculated for non-statin lipid lowering drugs. An increased disproportionality have been found for most individual statins lovastatin: [ROR: 14.80, 95% confidence interval (CI): 13.30, 16.46)], atorvastatin (ROR: 3.48, 95% CI 3.19-3.80), pravastatin (ROR: 3.15, 95% CI: 2.54-3.90), rosuvastatin (ROR: 2.90, 95% CI: 2.53-3.31), simvastatin (ROR: 2.27, 95%CI: 1.99-2.60), fluvastatin (ROR: 2.03, 95% CI: 1.33-3.08) and statins (overall) ROR: 3.66, 95% CI:3.46-3.86). Increased disproportionality for cataract and statins (drug-class) have been found regardless of statin lipophilicity, sex and group age (more or less than 65 years old). No disproportionality was found for other lipid-lowering drugs (ezetimibe, fibrates or PCSK9 inhibitors). These findings suggest an increased risk of cataract associated with statins as a drug-class. Further studies to characterize the risk are advised. Benefits and potential harms should be considered before starting treatment with statins.


Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Cataract/epidemiology , Drug Monitoring/statistics & numerical data , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Pharmacovigilance , Adolescent , Adult , Aged , Aged, 80 and over , Cataract/chemically induced , Child , Female , Humans , Incidence , Male , Middle Aged , Odds Ratio , Risk Assessment/methods , Young Adult
13.
High Blood Press Cardiovasc Prev ; 26(3): 199-207, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31236902

ABSTRACT

Proprotein convertase subtilisin/kexin type 9 (PCSK9)-related discoveries of the turn of the century have translated into substantial novelty in dyslipidemia treatment in the last 5 years. With chronic preventable atherosclerotic cardiovascular diseases (ASCVD) representing an epidemic of morbidity and mortality worldwide, low-density lipoprotein cholesterol (LDL-c) reduction represents a public health priority. By overcoming two major statin-related issues, namely intolerance and ineffectiveness, PCSK9 inhibitors have offered a safe and effective option in selected clinical settings where LDL-c reduction is required. Herein, we recapitulate recent findings, clinical applications, and ASCVD prevention potential of PCSK9 inhibition, with focus on anti-PCSK9 monoclonal antibodies, evolocumab and alirocumab.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Anticholesteremic Agents/therapeutic use , Atherosclerosis/prevention & control , Cholesterol, LDL/blood , Dyslipidemias/drug therapy , PCSK9 Inhibitors , Serine Proteinase Inhibitors/therapeutic use , Animals , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Anticholesteremic Agents/adverse effects , Atherosclerosis/blood , Atherosclerosis/enzymology , Atherosclerosis/epidemiology , Biomarkers/blood , Dyslipidemias/blood , Dyslipidemias/enzymology , Dyslipidemias/epidemiology , Humans , Practice Guidelines as Topic , Proprotein Convertase 9/metabolism , Risk Factors , Serine Proteinase Inhibitors/adverse effects , Treatment Outcome
15.
Rev. argent. cardiol ; 86(3): 103-109, jun. 2018.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1003195

ABSTRACT

RESUMEN: Introducción: La hipercolesterolemia familiar es una hiperlipidemia primaria. Se trata de un trastorno genético autosómico dominante del metabolismo de las lipoproteínas, caracterizado por concentraciones plasmáticas elevadas de colesterol unido a lipoproteínas de baja densidad y presencia de xantomas tendinosos, y está asociado con el desarrollo prematuro de enfermedad cardiovascular. Objetivos: Investigar la presencia de mutaciones en el principal gen asociado al desarrollo de hipercolesterolemia familiar (LDLR) en un grupo de pacientes identificados como "casos índices", de entre aquellos que concurren al Servicio de Lípidos del Hospital Universitario Fundación Favaloro con diagnóstico clínico de hipercolesterolemia familiar. Determinar la composición ancestral de la población estudiada. Material y métodos: Se estudió una población de 38 pacientes con diagnóstico clínico de hipercolesterolemia familiar. La región codificante y las zonas intrónicas adyacentes del gen LDLR se secuenciaron automáticamente por el método de Sanger. Se investigó el componente ancestral de la población estudiada a partir del análisis de 46 marcadores informativos de ancestralidad (AIM-Indel). Resultados: Se identificaron 50 variantes diferentes, de las cuales el 48% se consideraron patogénicas. Se logró establecer una correlación genotipo-gravedad del fenotipo en el 60,5% de los pacientes estudiados. El componente ancestral de la población estudiada fue predominantemente europeo, seguido de un componente nativo-americano y, en menor proporción, africano. Conclusiones: El análisis genético por secuenciación del gen LDLR en pacientes identificados como "casos índices" con diagnóstico clínico de hipercolesterolemia familiar permite correlacionar el dato genético con la gravedad del fenotipo observado clínicamente y efectuar un diagnóstico en cascada en los miembros de la familia que presentan los criterios de inclusión considerados.


ABSTRACT: Background: Familial hypercholesterolemia is a primary hyperlipidemia. It is an autosomal dominant genetic disorder of lipoprotein metabolism, characterized by elevated plasma low-density lipoprotein cholesterol and presence of tendon xanthomas, and is associated with early cardiovascular disease. Objectives: The aim of this study was to investigate the presence of mutations in the main gene associated with the development of familial hypercholesterolemia (LDLR) in a group of patients identified as "index cases" attending the Lipid Clinic of the Hospital Universitario Fundación Favaloro with clinical diagnosis of familial hypercholesterolemia. The ancestral composition of the study population was determined. Methods: We evaluated 38 patients with clinical diagnosis of familial hypercholesterolemia. Mutation screening of the LDLR gene coding regions and adjacent intronic areas was performed using Sanger sequencing. The ancestral component of the study population was investigated using 46 ancestry inference markers (AIM-Indel). Results: Fifty different variants were identified, 48% of which were considered pathogenic. A genotype-phenotype severity correlation was established in 60.5% of the patients evaluated. The ancestral component of the study population was predominantly European, followed by native-American and African in lower proportion. Conclusions: Genetic testing by LDLR gene sequencing in patients identified as "index cases" with clinical diagnosis of familial hypercholesterolemia allows the correlation between the genetic information and the severity of the clinical phenotype to a cascade testing of the family members presenting the inclusion criteria considered.

16.
Rev. argent. cardiol ; 86(2): 103-109, abr. 2018.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1003185

ABSTRACT

RESUMEN: Introducción: La hipercolesterolemia familiar es una hiperlipidemia primaria. Se trata de un trastorno genético autosómico dominante del metabolismo de las lipoproteínas, caracterizado por concentraciones plasmáticas elevadas de colesterol unido a lipoproteínas de baja densidad y presencia de xantomas tendinosos, y está asociado con el desarrollo prematuro de enfermedad cardiovascular. Objetivos: Investigar la presencia de mutaciones en el principal gen asociado al desarrollo de hipercolesterolemia familiar (LDLR) en un grupo de pacientes identificados como "casos índices", de entre aquellos que concurren al Servicio de Lípidos del Hospital Universitario Fundación Favaloro con diagnóstico clínico de hipercolesterolemia familiar. Determinar la composición ancestral de la población estudiada. Material y métodos: Se estudió una población de 38 pacientes con diagnóstico clínico de hipercolesterolemia familiar. La región codificante y las zonas intrónicas adyacentes del gen LDLR se secuenciaron automáticamente por el método de Sanger. Se investigó el componente ancestral de la población estudiada a partir del análisis de 46 marcadores informativos de ancestralidad (AIM-Indel). Resultados: Se identificaron 50 variantes diferentes, de las cuales el 48% se consideraron patogénicas. Se logró establecer una correlación genotipo-gravedad del fenotipo en el 60,5% de los pacientes estudiados. El componente ancestral de la población estudiada fue predominantemente europeo, seguido de un componente nativo-americano y, en menor proporción, africano. Conclusiones: El análisis genético por secuenciación del gen LDLR en pacientes identificados como "casos índices" con diagnóstico clínico de hipercolesterolemia familiar permite correlacionar el dato genético con la gravedad del fenotipo observado clínicamente y efectuar un diagnóstico en cascada en los miembros de la familia que presentan los criterios de inclusión considerados.


ABSTRACT: Background: Familial hypercholesterolemia is a primary hyperlipidemia. It is an autosomal dominant genetic disorder of lipoprotein metabolism, characterized by elevated plasma low-density lipoprotein cholesterol and presence of tendon xanthomas, and is associated with early cardiovascular disease. Objectives: The aim of this study was to investigate the presence of mutations in the main gene associated with the development of familial hypercholesterolemia (LDLR) in a group of patients identified as "index cases" attending the Lipid Clinic of the Hospital Universitario Fundación Favaloro with clinical diagnosis of familial hypercholesterolemia. The ancestral composition of the study population was determined. Methods: We evaluated 38 patients with clinical diagnosis of familial hypercholesterolemia. Mutation screening of the LDLR gene coding regions and adjacent intronic areas was performed using Sanger sequencing. The ancestral component of the study population was investigated using 46 ancestry inference markers (AIM-Indel). Results: Fifty different variants were identified, 48% of which were considered pathogenic. A genotype-phenotype severity correlation was established in 60.5% of the patients evaluated. The ancestral component of the study population was predominantly European, followed by native-American and African in lower proportion. Conclusions: Genetic testing by LDLR gene sequencing in patients identified as "index cases" with clinical diagnosis of familial hypercholesterolemia allows the correlation between the genetic information and the severity of the clinical phenotype to a cascade testing of the family members presenting the inclusion criteria considered.

17.
Rev. Nutr. (Online) ; 31(2): 137-145, Mar.Apr. 2018. tab
Article in English | LILACS | ID: biblio-1041253

ABSTRACT

ABSTRACT Objective To compare the effects of fermented kefir on the nutritional, physiological, and biochemical parameters of rats. Methods Grains of milk kefir (whole and skimmed) and water kefir (brown sugar) were used. The chemical composition analysis was performed on substrates and fermented beverages. The rats were evaluated for weight gain, body mass index, as well as their food, water, kefir, and calorie intake. We also evaluated their energy efficiency coefficient, weight of organs, in addition to their serum, and hepatic biochemistry. Results Fermentation increased the acid content index owing to degradation of lactose and brown sugar. The animals consumed more kefir, reducing the intake of chow and water. Kefir did not alter body and organ weight, while improving the lipid profile. Conclusion Water kefir with brown sugar was more effective in improving the lipid profile.


RESUMO Objetivo Este estudo tem como objetivo comparar os efeitos dos fermentados de kefir sobre parâmetros nutricionais, fisiológicos e bioquímicos de ratos. Métodos Foram utilizados grãos de kefir de leite (integral e desnatado) e de água (açúcar mascavo). A composição química foi realizada nos substratos e fermentados. Foram avaliados nos ratos: ganho de peso; índice de massa corporal; ingestão de ração, água, kefir e calorias; coeficiente de eficiência energética; peso dos órgãos; e bioquímica sérica e hepática. Resultados A fermentação elevou o índice de compostos ácidos a partir da degradação da lactose e do açúcar mascavo. Os animais consumiram mais kefir, diminuindo a ingestão de ração e água. O kefir não alterou o peso corporal e dos órgãos, melhorando ainda o perfil lipídico. Conclusão O kefir de água com açúcar mascavo foi mais eficaz na melhora do perfil lipídico.


Subject(s)
Animals , Rats , Cholesterol , Rats, Wistar , Dietary Sucrose , Fermentation , Kefir , Anticholesteremic Agents
18.
BMC Med ; 16(1): 5, 2018 01 11.
Article in English | MEDLINE | ID: mdl-29321031

ABSTRACT

BACKGROUND: The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice. METHODS: In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40-70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data. RESULTS: Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P < 0.05). Cost and quality-adjusted life years did not differ between the groups. CONCLUSIONS: The results of the ECSTATIC study show that an attempt to deprescribe preventive cardiovascular medication in low-CVD-risk patients is safe in the short term when blood pressure and cholesterol levels are monitored after stopping. An attempt to deprescribe medication can be considered, taking patient preferences into consideration. TRIAL REGISTRATION: This study was registered with Dutch trial register on 20 June 2012 ( NTR3493 ).


Subject(s)
Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/prevention & control , Chemoprevention , Deprescriptions , General Practice/statistics & numerical data , Adult , Aged , Antihypertensive Agents/therapeutic use , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Chemoprevention/methods , Chemoprevention/statistics & numerical data , Cluster Analysis , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Primary Prevention/methods , Prognosis , Quality-Adjusted Life Years , Risk Factors
19.
Patient Prefer Adherence ; 11: 975-984, 2017.
Article in English | MEDLINE | ID: mdl-28579760

ABSTRACT

BACKGROUND: Patients with low cardiovascular disease (CVD) risk potentially use preventive cardiovascular medication unnecessarily. Our aim was to identify various viewpoints and beliefs concerning the preventive CVD management of patients with low CVD risk using preventive cardiovascular medication. Furthermore, we investigated whether certain viewpoints were related to a preference for deprescription or the continuation of preventive cardiovascular medication. METHODS: In 2015, we purposively sampled patients from the intervention arm of the Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care (ECSTATIC) trial in the Netherlands for this study. Participants made Q-sorts by ranking 43 statements concerning preventive CVD management from "totally disagree" to "totally agree". These Q-sorts were analyzed using PQMethod 2.35 software. A varimax procedure presented the distinguishing viewpoints that were favored by our participants. We used group discussion quotations to underline our findings. For validation purposes, we asked participants how well each viewpoint fitted them. RESULTS: Of 291 invited patients, 33 participated. Thirty-one Q-sorts were analyzed. The following three viewpoints were found: 1) a controlling viewpoint, in which patients held the belief that monitoring blood pressure and cholesterol levels is important (n=13, of which seven had their medication deprescribed and six continued their medication); 2) an autonomous viewpoint, in which patients showed a dislike of medication (n=8, of which seven had their medication deprescribed and one had it continued); and 3) an afraid viewpoint, in which patients were fearful of developing CVD (n=8, of which two had their medication deprescribed and six had it continued). Seventy-four percent of the participants believed that the viewpoint to which they were assigned was a good fit. CONCLUSION: Three well-discriminating viewpoints about preventive CVD management were determined. Knowing and recognizing these viewpoints is effective for general practitioners when discussing the deprescribing of preventive cardiovascular medications with patients and may be used to promote implementation of deprescription.

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