Changing the conversation from ‘chronic disease’ to ‘chronic health’

Despite spectacular advancements in pharmacological and interventional treatments for cardiovascular disease (CVD), it remains the leading cause of morbidity, disability, and premature death worldwide, the costs of which are unsustainable in all healthcare systems. Lifetime risk of a first CVD event at age 50 is ∼65% in men, and it is increasingly affecting younger women and men. Atherosclerosis is the underlying cause of ∼90% of cases of myocardial infarction, 60% of strokes, most cases of chronic heart failure, peripheral arterial disease, and many cases of dementia. The evidence that an ageing, increasingly sedentary, sleep deprived and psychologically challenged population consuming hypercaloric diets rich in animal and ultraprocessed food since conception is likely responsible for this is substantial. The opportunity to intervene exists many years before presentation in middle age and our failure to act effectively is alarming. The current pandemic has disrupted health systems worldwide and renewed interest in, and appreciation of, the critical importance of lifestyle over an individual’s lifetime to deliver affordable improvements in health and healthy ageing. Into the frame of the problem comes a renewed focus on digital health and educational solutions delivered with precision in a personalized way.

Evidence that lifestyle changes markedly improve cardiovascular outcomes including reduced disability and improved longevity in asymptomatic and known CVD is overwhelming. The actual change needed to achieve benefit is remarkably small which makes our failure to achieve it in the real world so much more compelling. The CALERIE trial showed that in non-obese middle aged men and women, a modest 13% calorie restriction maintained adequate nutrition while reducing inflammation, oxidative stress and improved all classical cardiometabolic risk factors well below the conventional risk thresholds used in clinical practice.¹ Participants in the Framingham Study with cardiovascular factors similar to those achieved by CALERIE volunteers had a 5% risk of developing CVD, whereas those with two or more abnormal factors had a 69% probability and lived ∼11 years less.²

In lifestyle prevention studies, the UK DiRECT³ and Cuban trial⁴ have shown that remission occurs in ∼80% of patients affected by type 2 diabetes and NAFLD who lost >10 kg, and in those with diabetic nephropathy small reductions in body weight significantly reduce glomerular hyperfiltration, albuminuria, inflammation, and multiple other cardiometabolic risk factors.⁵ The Pridimed, the Lyon, and Indo-Mediterranean Diet Heart trials have demonstrated a powerful protective effect of a Mediterranean-style diet against major cardiovascular events, including stroke in high-risk patients, coronary recurrence rate, and sudden cardiac death in those who already suffered from a prior myocardial infarction.⁶ Recent and accumulating work in animal models and humans indicates that specific dietary manipulations (e.g. intermittent fasting, time-restricted feeding, single-nutrient modifications) in conjunction with different forms of exercise training, mindfulness-based stress reduction, and sleep-promoting interventions can also play a role in preventing or slowing the accumulation of molecular damage leading to cardiovascular dysfunction.⁷

Despite the clear experimental animal, epidemiological, and clinical trial data demonstrating the power of lifestyle to alter cardiometabolic risk factors and events (Figure 1), we see two clear gaps which need to be addressed. First, there is a need for more mechanistic studies to understand the magnitude and temporal effects of different lifestyle interventions on coronary macro- and microvascular structure and function, myocardial inflammation, and fibrosis. Computed tomography coronary angiography (CTCA) coupled with AI-assisted algorithms and radiomic plaque analysis is emerging as a powerful non-invasive tool to quantify not only the coronary calcium score but also the volume and structure of low attenuation non-calcified plaques, and pericoronary adipose tissue. Several studies have tracked the positive impact of various pharmacological therapies on atheroma volume and characteristics on CTCA, and early evidence suggests that lifestyle intervention may yield changes observable as early as 12 months.⁸ Moreover, state-of-the-art MRI techniques can provide quantitative non-invasive characterization of acute or chronic ischaemic and non-ischaemic scar, coronary microvascular dysfunction and spasm, focal and global myocardial inflammation, and diastolic function at rest and during adenosine stress or exercise. Further work is warranted to explore the relationships between lifestyle-induced imaging phenotypes and the results of multi-omics analyses (transcriptome, methylome, metabolome, proteome, phosphoproteome, microbiome) to develop a meta-phenotypic map across multiple scales of responses.

Figure 1

Many prevalent cardiometabolic diseases share a common metabolic substrate. Unhealthy lifestyle effectors, including excessive calorie intake, unhealthy diet, sedentary lifestyle, mental stress, smoking, and pollution, modulate important metabolic, hormonal and immune factors associated with the development of cardiovascular disease.

The second critical and rate limiting step is to change how we engage individuals and whole populations in implementing these interventions in the ‘real world’. A fundamental shift in our own approach is needed so we change our conversation from the fear and pessimism of ‘disease’ to one of the optimism about health. The power of personalized data and digital health and educational tools can empower individuals to engage with the lifestyle changes they need as individuals and track the changes, which result from it in almost real time.

Currently, intensive lifestyle intervention trials lack applicability, scalability, and affordability to deliver their outcomes in most healthcare settings. While primary care doctors have tremendous influence on their patients’ lifestyle, they lack time, and the latest evidence-based knowledge and effective tools to deliver sustainable and effective behavioural and educational interventions to patients at scale. Smartphone technology can address some of these issues and represent a key advance on previous text-message and telehealth based technologies. There has been an exponential rise in smartphone and wearable use over the past decade, which has the potential to revolutionize CVD prevention and management. Smartphone interventions are attractive and engaging for clinicians, healthcare workers, and patients alike can be started immediately and can be delivered at anytime from anywhere. Smartphone delivery of cardiac rehabilitation can be delivered much more effectively than traditional face-to-face cardiac rehabilitation, with enhanced uptake (94% vs. 68%, P < 0.05) and completion (80% vs. 47%, P < 0.05) being significantly higher with smartphone delivery.⁹

To address the aforementioned challenges we are running the LIVEPLUS trial (Figure 2). Over 12 months, we will measure the effect of an intense lifestyle intervention (5:2 pescovegetarian diet, physical activity, and stress reduction) on two primary imaging endpoints including CTCA low attenuation plaque volume and structure, and myocardial blood flow, and diastolic function by stress MRI. We will also measure a number of other key genomic, metabolomic, immune, and gut microbiome-related adaptations, which will help us to elucidate how these changes interact with imaging endpoints. To trial this intervention, we have built a smartphone app and digital health ecosystem. Such a digital solution, if proven to be effective is translational and scalable to use in clinical practice and as an educational tool for healthcare professionals.

Figure 2

LIVEPLUS randomized clinical trial. LIVEPLUS is a mechanistic-based lifestyle intervention with a digital health solution. Primary outcomes are change in: (i) CTCA low attenuation plaque volume and structure and (ii) myocardial blood flow by stress MRI. Quantification of myocardial blood flow is a novel tool, which is now possible via automated in-line perfusion mapping techniques on CMR. We do not know how well non-obstructive plaque correlates with changes in myocardial blood flow, nor how a multifaceted lifestyle intervention may impact microvascular dysfunction, cardiac inflammation, and stiffness. We will also measure liver fibrosis and inflammation by MRI, flow-dependent vasodilation of the brachial artery, arterial stiffness by pulse wave velocity, heart rate variability, and key genomic, metabolomic, immune, and gut microbiome-related adaptations. The app contains evidence-based lifestyle education, the ability to set goals, join a social network, real-time feedback, motivation, reminders. It is integrable with wearables, meaning that individual behaviour can be monitored and personalized automatically via ‘just-in-time’ adaptive interventions.¹⁰

Conclusion

The time has come for a change in the conversation about chronic disease to a refreshed and repurposed model of health care, which emphasizes the power of prevention using the best evidence we have to change potential to actual outcomes. We can now combine ubiquitous wearable-derived data with evidence-based digital health interventions to effect ‘change we and our patients can believe in’. Population health approaches have emphasized a ‘top down’ approach but we hope that a ‘bottom up’ or individual and personalized care approach will melt up to the health care we seek for individuals, which the population and healthcare systems of the future can afford and, therefore, sustain. The LIVEPLUS app exemplifies a step in a longer journey to empower a fundamental change in the conversation from ‘chronic disease’ to ‘chronic health’.

Acknowledgements

The authors apologize for the omission of relevant work owing to space constraints.

Funding

L.F. is supported, and this work was carried out by funding from the Australian NHMRC Investigator Grant (APP1177797), Australian Youth and Health Foundation, Philip Bushell Foundation, and Bakewell Foundation.

Conflict of interest: The authors declare no conflict of interest.

Data availability

No new data were generated or analysed in support of this research.