Modifying genetic susceptibility to coronary heart disease through an integrated plant-based diet-lifestyle

Cardiovascular disease prevention has traditionally relied on broad lifestyle recommendations, while advances in genetic epidemiology have raised questions about the extent to which inherited susceptibility might limit their effectiveness. In this context, understanding whether healthy lifestyle patterns can meaningfully modify coronary heart disease risk across different levels of genetic predisposition remains a central challenge.¹ In this issue of The Lancet Regional Health – Europe, Wang and colleagues address this question by examining the joint association of genetic risk and adherence to a healthy plant-based diet integrated with key lifestyle behaviours, as outlined in the American Heart Association's Life's Essential 8 framework.² Using data from a large population-based cohort, the authors show that higher adherence to the hPDI–Lifestyle score is associated with a substantially lower incidence of coronary heart disease across all genetic risk strata, with the greatest relative risk reduction observed among individuals at high genetic risk. These findings demonstrate that genetic susceptibility to coronary heart disease can be meaningfully modified through adherence to an integrated plant-based diet–lifestyle pattern.³

Previous research examining the interplay between lifestyle and genetic risk for coronary heart disease has often addressed these domains in a fragmented manner, analysing dietary patterns, lifestyle behaviours, or genetic susceptibility largely in isolation.⁴ Even when combined, lifestyle factors have frequently been treated as covariates rather than as an integrated exposure, and dietary quality has rarely been conceptualised within a broader behavioural framework. In this context, the approach adopted by Wang and colleagues represents a meaningful advance. By integrating a healthy plant-based diet with a set of key lifestyle behaviours into a single composite score, the authors capture the cumulative and interrelated nature of behaviours known to influence cardiovascular risk. This holistic framework moves beyond reductionist models and provides a more realistic representation of how diet and lifestyle operate together to shape disease risk across genetic strata.²

Beyond its epidemiological relevance, these findings carry important clinical and public health implications. The observation that high adherence to a healthy plant-based diet-lifestyle is associated with lower coronary risk even among individuals with elevated genetic susceptibility challenges deterministic interpretations of genetic risk. Rather than supporting genetically tailored restrictions on preventive strategies, the results reinforce the continued relevance of population-wide lifestyle recommendations, while also opening the door to more nuanced risk communication.⁵ In clinical practice, genetic information could be leveraged not to stratify access to prevention, but to motivate and prioritise lifestyle interventions in individuals at higher inherited risk. At a population level, the integrated nature of the score underscores the need for preventive frameworks that move beyond single-behaviour targets and instead promote comprehensive lifestyle patterns as a cornerstone of cardiovascular disease prevention.⁶

Despite its strengths, several important questions remain. As with most large-scale observational studies, the associations reported by Wang and colleagues cannot establish causality, underscoring the need for longitudinal assessments that capture changes in lifestyle patterns over time and their dynamic relationship with coronary risk. Whether improvements or deteriorations in adherence to this integrated score translate into proportional changes in disease incidence remains unknown. Moreover, interventional studies specifically designed to modify lifestyle behaviours according to genetic risk profiles could provide critical evidence to move beyond association and better inform prevention strategies. Finally, linking such integrated lifestyle scores to intermediate phenotypes—particularly markers of subclinical atherosclerosis such as coronary artery calcium—may help clarify the biological pathways through which genetic and behavioural factors jointly influence coronary heart disease risk.

Taken together, the findings discussed here highlight the need to move beyond fragmented views of cardiovascular prevention and towards integrative frameworks that reflect the complexity of real-world cardiovascular risk. Future research should aim to refine and validate composite lifestyle scores across diverse populations, incorporate repeated assessments over time, and test their responsiveness to targeted interventions. Integrating genetic risk with longitudinal lifestyle data and intermediate disease phenotypes may ultimately provide a more comprehensive understanding of coronary heart disease pathophysiology, while informing prevention strategies that are both biologically grounded and broadly applicable. In this regard, the work by Wang and colleagues represents an important step towards a more integrated and actionable model of cardiovascular risk prevention.

Contributors

F.M. Gutiérrez-Mariscal: Literature search, conceptualization, writing-original draft, supervision.

J. López-Miranda: Writing-review & editing, supervision.

Declaration of interests

F.M. Gutiérrez-Mariscal declares no conflicts of interest related to the content of this manuscript. J. López-Miranda reports having received fees for consultancy, lectures, and educational activities from Amgen, Sanofi, MSD, Daiichi Sankyo, Novartis, and Laboratorios Dr. Esteve, not related to the subject matter of this manuscript.