Genetics partly influence the shape of the heart’s left and right ventricles, a study shows for the first time, with the findings potentially helping to refine cardiovascular disease (CVD) risk assessment in clinical settings.
Variations in heart shape were more strongly related to cardiovascular risk factors and more predictive of major adverse cardiovascular events than traditional measures of cardiac structure such as mass and volume, researchers wrote in the journal Nature Communications.
‘Genetic associations with heart shape variation may therefore provide information not found from genetic analyses on standard cardiac structural phenotypes and may assist in understanding the mechanisms underlying the development of CVD,’ they said.
The UK and Spanish research team used cardiac magnetic resonance images from 45,683 individuals from the UK Biobank – a large-scale biomedical database and research resource – to create 3D models of hearts before using principal component analysis (PCA) to examine the characteristics of heart shapes.
The analysis identified principal components including heart size, apex-base length and anterior-posterior width.
Genome-wide associated studies were then performed on the first 11 principal components, that captured 83.6% of shape variance, reported the researchers from King’s College London, Queen Mary University of London, and University College London, UK, and University of Zaragoza and University Hospital of A Coruña, Spain.
Through this statistical analysis, they identified 43 significant genomic loci, 14 of which were previously unreported for cardiac traits.
‘This is the first study to examine the genetic architecture of multi-dimensional biventricular heart shape using PCA,’ they wrote.
Most of the principal components were found to be moderately heritable, consistent with previous traditional measures of cardiac structure.
The principal components also demonstrated significant associations with cardiometabolic diseases, including atrial fibrillation and myocardial infarction.
Study co-author Professor Patricia B. Munroe, professor of molecular medicine and centre lead for clinical pharmacology and precision medicine at Queen Mary University of London, said the study provided new information about how researchers considered CVD risk.
‘We’ve long known that size and volume of the heart matter, but by examining shape, we’re uncovering new insights into genetic risks,’ she said.
‘This discovery could provide valuable additional tools for clinicians to predict disease earlier and with more precision.’
Dr Richard Burns, statistical geneticist at Queen Mary University of London, said: ‘This study sets an important foundation for the exploration of genetics in both ventricles. The study confirms that combined cardiac shape is influenced by genetics, and demonstrates the usefulness of cardiac shape analysis in both ventricles for predicting individual risk of cardiometabolic diseases alongside established clinical measures.’
The researchers are keen for further studies to be undertaken on how these findings could be integrated into clinical practice.
And future research could also further examine the anatomical cardiac shape features informed by the identified principal components, they suggested.
Mechanistic studies are also needed to examine the direction of effect between multidimensional heart shape and cardiometabolic disease, the researchers added, including further exploration of the functionality of the identified candidate genes.
The findings follow another study drawing on UK Biobank data published earlier this month which found adults who have irregular sleep patterns were 26% more likely to have a major cardiovascular event than those with a regular sleep-wake cycle.
Published in the Journal of Epidemiology & Community Health, the researchers designed an observational study involving 72,269 people from the UK Biobank aged between 40 and 79 with no history of cardiovascular disease.
For moderately irregular sleepers, meeting sleep duration recommendations could largely offset the elevated risk of cardiovascular events, the researchers found.
