Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women

Autor: Richard J. Sinke, M. Viel, Xiang Zhang, Roan Kanninga, Antoine Rimbert, Jan Albert Kuivenhoven, Freerk van Dijk, Peter J. Lansberg, J.W. Balder
Přispěvatelé: Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), APH - Methodology, Graduate School, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Diabetes & metabolism, ACS - Atherosclerosis & ischemic syndromes
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Adult
DNA copy number variations
lifestyle
hypobetalipoproteinemias
Low density lipoprotein cholesterol
Physiology
UNITED-STATES
Familial hypercholesterolemia
030204 cardiovascular system & hematology
LDL-CHOLESTEROL
lipids
03 medical and health sciences
0302 clinical medicine
Physiology (medical)
SEQUENCE VARIATION
Medicine
Humans
risk factors
PARTICIPANTS
CORONARY-HEART-DISEASE
Sequence variation
Risk factor
FAMILIAL HYPERCHOLESTEROLEMIA
Life Style
Lipoprotein cholesterol
Ldl cholesterol
GENERAL-POPULATION
RISK
hypercholesterolemia
business.industry
Clinical events
MUTATIONS
Cholesterol
LDL
ASSOCIATION
medicine.disease
Atherosclerosis
Coronary heart disease
lipoproteins
030104 developmental biology
Female
lipids (amino acids
peptides
and proteins)
Cardiology and Cardiovascular Medicine
business
Algorithms
Zdroj: Circulation, 137(8), 820-831. LIPPINCOTT WILLIAMS & WILKINS
Circulation, 137(8), 820-831. Lippincott Williams and Wilkins
ISSN: 0009-7322
DOI: 10.1161/circulationaha.117.032479
Popis: Background: Atherosclerosis starts in childhood but low-density lipoprotein cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when clinical events have occurred. Women are usually affected later in life than men and are underdiagnosed, undertreated, and understudied in cardiovascular trials and research. This study aims at a better understanding of lifestyle and genetic factors that affect LDL-C in young women. Methods: We randomly selected for every year of age 8 women with LDL-C ≤1st percentile (≤50 mg/dL) and 8 women with LDL-C ≥99th percentile (≥186 mg/dL) from 28 000 female participants aged between 25 to 40 years of a population-based cohort study. The resulting groups include 119 and 121 women, respectively, of an average 33 years of age. A gene-sequencing panel was used to assess established monogenic and polygenic origins of these phenotypes. Information on lifestyle was extracted from questionnaires. A healthy lifestyle score was allocated based on a recently developed algorithm. Results: Of the women with LDL-C ≤1st percentile, 19 (15.7%) carried mutations that are causing monogenic hypocholesterolemia and 60 (49.6%) were genetically predisposed to low LDL-C on the basis of an extremely low weighted genetic risk score. In comparison with control groups, a healthier lifestyle was not associated with low LDL-C in women without genetic predispositions. Among women with LDL-C ≥99th percentile, 20 women (16.8%) carried mutations that cause familial hypercholesterolemia, whereas 25 (21%) were predisposed to high LDL-C on the basis of a high-weighted genetic risk score. The women in whom no genetic origin for hypercholesterolemia could be identified were found to exhibit a significantly unfavorable lifestyle in comparison with controls. Conclusions: This study highlights the need for early assessment of the cardiovascular risk profile in apparently healthy young women to identify those with LDL-C ≥99th percentile for their age: first, because, in this study, 17% of the cases were molecularly diagnosed with familial hypercholesterolemia, which needs further attention; second, because our data indicate that an unfavorable lifestyle is significantly associated with severe hypercholesterolemia in genetically unaffected women, which may also need further attention.
Databáze: OpenAIRE
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