Five classic risk factors are responsible for about half of the global cardiovascular disease (CVD) burden. A major new analysis from the Global Cardiovascular Risk Consortium, published in the New England Journal of Medicine, has quantified the profound impact of these factors on lifetime estimates of CVD and all-cause mortality, revealing that their absence at midlife is associated with more than a decade of additional life expectancy.¹

This large-scale analysis (NCT05466825) harmonised individual-level data from 2,078,948 participants across 133 cohorts, spanning 39 countries and six continents. The researchers estimated the lifetime risk of CVD and death from any cause up to 90 years of age. This was stratified according to the presence or absence of five key risk factors assessed at 50 years of age: arterial hypertension, hyperlipidemia, underweight and overweight or obesity, diabetes, and smoking. The study also calculated the differences in life span free of CVD or death based on risk factor profiles and analysed risk-factor trajectories to predict the impact of midlife modifications.

The study found a stark contrast in outcomes based on risk factor status. For individuals with all five risk factors present at age 50, the lifetime risk of developing CVD was 24% (95% CI, 21 to 30) for women and 38% (95% CI, 30 to 45) for men.

In a direct comparison between participants with no risk factors and those with all five, the absence of these factors translated into a substantial gain in healthy years. Women with no risk factors gained an estimated 13.3 additional life-years free of CVD (95% CI, 11.2 to 15.7), while men gained 10.6 years (95% CI, 9.2 to 12.9). The benefit for overall survival was even greater, with an estimated 14.5 additional life-years free of death for women (95% CI, 9.1 to 15.3) and 11.8 years for men (95% CI, 10.1 to 13.6).

Furthermore, modifying risk factors in midlife (age 55 to <60 years) was highly beneficial. Modifying hypertension was associated with the greatest gain in CVD-free years, while modifying smoking was linked to the most additional years free from death.

These findings provide robust, global evidence of the long-term benefits of maintaining a favourable cardiovascular risk profile by midlife. The Global Cardiovascular Risk Consortium concluded, "The absence of five classic risk factors at 50 years of age was associated with more than a decade greater life expectancy than the presence of all five risk factors, in both sexes."¹ This powerful data reinforces the critical importance of preventive cardiology and provides tangible figures that can be used in patient counselling to motivate lifestyle changes and adherence to treatment. An accompanying editorial highlights that while these estimates are a vital tool, the challenge remains in translating this knowledge into effective clinical practice and public health action.² The results particularly emphasise the high-impact potential of managing hypertension and promoting smoking cessation in the middle-aged population.

References

1. The Global Cardiovascular Risk Consortium. Global Effect of Cardiovascular Risk Factors on Lifetime Estimates. N Engl J Med 2025;393:125-138. https://doi.org/10.1056/NEJMoa2415879

2. Mensah GA. Estimates of Cardiovascular Risks and Benefits — When Knowing Is Not Enough. N Engl J Med. 2025;393(2):187-189. https://doi.org/10.1056/NEJMe2504947

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