“The missing millions” conveys the pressing attention now put on a large group in the general population with unassessed disease risk, and in worryingly oblivious trajectories. The lay public often believe themselves to be “healthy” whilst not diagnosed with disease, although the reality is much more a wide continuum. Sudden unexpected, sometimes fatal, myocardial infarction (MI) among the young (50-60s) working age group of Singaporeans is attracting growing attention, with increasingly frequent reports on the news. In Singapore and globally, and despite key investment in medicines for hypertension and hyperlipidemia, CVD remains a top cause of death. Lifestyle largely explains why CVD still claims ~17.9 million lives worldwide every year. Even as patients survive an acute MI, they have a high likelihood of heart failure (HF) in later years. CVD can cut short an adult life in its prime, and also cause chronic ill health in the silver years of the increasingly ageing population.

The CV clinician scientists and researchers in Singapore have invested major effort through large collaborative grants in past years, focusing on patients with HF and MI, deeply characterising the clinical sub-groups. We have established important observations including a unique Asian heart disease patient profile, buttressed by a very prominent metabolic syndrome co-morbidity, more significant than seen in the west, and occurring most commonly in lean (lower BMI) yet centrally obese (higher waist-to-height ratio) individuals. HF presents at a younger age in Singapore (~10y younger than the west), has worse clinical outcomes, and left ventricular (LV) decompensation is dominantly driven by metabolic dysfunction, often independently of coronary artery disease (CAD) or MI. In line with the new Singapore RIE2025 research objective, we are answering the call to go upstream, and widen now to achieve early detection and early prevention of CVD.

Theme 1  To assemble a cohort for (a) cardiovascular, (b) liver, (c) metabolic, (d) molecular and (e) digital lifestyle characterisation. The RESET cohort “Redirecting lipid, immune and metabolic drivers of early CVD” (N=3000).
Theme 2 To map the clinical, molecular, and digital lifestyle associations, trajectories and outcomes in RESET
Theme 3 To discover new targets in early CVD and validate mechanistic causality with mouse and human cell platforms (“reverse translation”)
Theme 4 To carry out a nested RCT of a digitally supported lifestyle intervention, incorporating behavioural, implementation and economic evaluations