ABSTRACT
Familial hypercholesterolemia (FH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes. A pathological variant has not been identified in 30-70% of clinically diagnosed FH patients, and a burden of LDL cholesterol (LDL-c)-raising alleles has been hypothesized as a potential cause of hypercholesterolemia in these patients. Our aim was to study the distribution of weighted LDL-c-raising single-nucleotide polymorphism (SNP) scores (weighted gene scores or wGS) in a population recruited in a clinical setting in Catalonia. The study included 670 consecutive patients with a clinical diagnosis of FH and a prior genetic study involving 250 mutation-positive (FH/M+) and 420 mutation-negative (FH/M-) patients. Three wGSs based on LDL-c-raising variants were calculated to evaluate their distribution among FH patients and compared with 503 European samples from the 1000 Genomes Project. The FH/M- patients had significantly higher wGSs than the FH/M+ and control populations, with sensitivities ranging from 42% to 47%. A wGS based only on the SNPs significantly associated with FH (wGS8) showed a higher area under the receiver operating characteristic curve, and higher diagnostic specificity and sensitivity, with 46.4% of the subjects in the top quartile. wGS8 would allow for the assignment of a genetic cause to 66.4% of the patients if those with polygenic FH are added to the 37.3% of patients with monogenic FH. Our data indicate that a score based on 8 SNPs and the75th percentile cutoff point may identify patients with polygenic FH in Catalonia, although with limited diagnostic sensitivity and specificity.
ABSTRACT
El estilo de vida es un concepto complejo que incluye los aspectos externos a nosotros mismos que pueden modular e influir en nuestra salud. Los conocimientos sobre la relación entre el estilo de vida y el riesgo cardiovascular están lejos de proporcionar los niveles de evidencia que se han conseguido con los ensayos clínicos con fármacos, debido a que los estudios son escasos, fundamentalmente de tipo observacional y en grandes cohortes, con la dificultad añadida de la no existencia de métodos seguros para conocer con precisión la ingesta diaria o lo largo de tiempo, así como la dificultad en la recogida de datos y en la medición de la adherencia debido a diferencias en la composición de los alimentos en distintas épocas y a la conducta alimentaria cambiante que posee el ser humano a lo largo del tiempo. En este documento nos hemos propuesto llevar a cabo una revisión actualizada y jerarquizada en base a las evidencias actuales, prestando atención a tres aspectos que tienen gran importancia patogénica y que podemos modificar directamente: la actividad física, el consumo de tabaco y el patrón de alimentación. Con ello pretendemos actualizar los nuevos conocimientos sobre su relación con el riesgo cardiovascular aportando evidencias útiles, constituyendo una herramienta sencilla dirigida especialmente a todos los profesionales de la salud implicados en el cuidado de personas con riesgo cardiovascular para trasladarlos a la práctica clínica, definiendo unas líneas de actuación sencillas y fáciles para ser transmitidas a las personas que reciban un consejo para la prevención primaria y secundaria de las enfermedades cardiovasculares
Lifestyle is a complex concept that includes aspects external to ourselves that can modulate and influence our health. The knowledge of the relationship between lifestyle and cardiovascular risk does not attain the level of evidence achieved with clinical trials with drugs, because clinical studies are scarce and mainly of observational nature, albeit based on large cohorts. Nutritional epidemiology has the added difficulty of being based mostly on subjective dietary recall methods to ascertain nutrient and food intake over time, with the additional problems of incomplete data collection, variable measurements of adherence due to seasonal and geographical differences in food composition, and the changing eating behavior that human beings have over time. The purpose of this document is to carry out an updated and hierarchical review of the relationship between lifestyle and cardiovascular disease based on current evidence, paying attention to three aspects that are of great pathogenic importance and are directly modifiable: physical activity, tobacco consumption, and diet. With this, we intend to update the knowledge on this relationship, construct evidence-based recommendations, and provide a simple tool for clinical practice especially directed to health professionals involved in the care of people at cardiovascular risk, defining simple and easy strategies for individuals who receive advice for the primary and secondary prevention of cardiovascular diseases
Subject(s)
Humans , Cardiovascular Diseases/prevention & control , Life Style , 24457 , Diet, Mediterranean , Exercise/physiology , Tobacco Use Disorder/complications , Alcohol Drinking/adverse effects , Functional Food , Risk FactorsABSTRACT
Lifestyle is a complex concept that includes aspects external to ourselves that can modulate and influence our health. The knowledge of the relationship between lifestyle and cardiovascular risk does not attain the level of evidence achieved with clinical trials with drugs, because clinical studies are scarce and mainly of observational nature, albeit based on large cohorts. Nutritional epidemiology has the added difficulty of being based mostly on subjective dietary recall methods to ascertain nutrient and food intake over time, with the additional problems of incomplete data collection, variable measurements of adherence due to seasonal and geographical differences in food composition, and the changing eating behavior that human beings have over time. The purpose of this document is to carry out an updated and hierarchical review of the relationship between lifestyle and cardiovascular disease based on current evidence, paying attention to three aspects that are of great pathogenic importance and are directly modifiable: physical activity, tobacco consumption, and diet. With this, we intend to update the knowledge on this relationship, construct evidence-based recommendations, and provide a simple tool for clinical practice especially directed to health professionals involved in the care of people at cardiovascular risk, defining simple and easy strategies for individuals who receive advice for the primary and secondary prevention of cardiovascular diseases.
Subject(s)
Cardiovascular Diseases/prevention & control , Health Behavior , Life Style , Cardiovascular Diseases/etiology , Diet , Exercise/physiology , Humans , Risk Factors , Tobacco Use/adverse effectsABSTRACT
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