
Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women
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.
- Jan-Willem Balder
- Antoine Rimbert
- Xiang Zhang
- Martijn Viel
- Roan Kanninga
- Freerk van Dijk
- Peter Lansberg
- Richard Sinke
- Jan Albert Kuivenhoven
Circulation. 2018;137:820-831, originally published February 19, 2018
Last modified: | 22 February 2018 07.59 a.m. |
More news
-
12 September 2023
Art in times of AI
Leonardo Arriagada Beltran conducted his PhD research on the interface of computer-generated art and the constantly evolving field of Artificial Intelligence (AI). He will defend his Phd thesis on 21 September. His research offers valuable insights...
-
28 August 2023
Harish Vedantham and Casper van der Kooi nominated for 'Wetenschapstalent 2023'
Harish Vedantham and Casper van der Kooi have been nominated by New Scientist for Wetenschapstalent 2023 (Science Talent 2023). This election is meant to give young scientists and their research a stage.
-
26 July 2023
Five promising UG researchers to top institutes abroad on Rubicon grants
No less than five promising PhD graduates from the University of Groningen will be able to conduct research at top institutes abroad for two years thanks to the Rubicon programme organized by the Netherlands Organisation for Scientific Research...