Key Points
- Five classic risk factors – HTN, DM, HLD, underweight/obesity, and smoking – account for 50% of the global burden of CV disease.
- The purpose of this global epidemiological study was to estimate the effect of these risk factors on the lifetime risk of CV disease and all-cause mortality and to quantify the years of life gained by avoiding or modifying these risk factors, in order to inform prevention strategies worldwide, using harmonized individual-level data from the Global Cardiovascular Risk Consortium, which included over 2 million participants from 39 countries and 8 geographic regions.
- Absence of all five risk factors at age 50 was associated with up to 13.3 additional years free of CV disease and 14.5 additional years of life compared to having all risk factors at age 50 for women, and 10.6 and 11.8 years for men, respectively.
- Treating hypertension between ages 50-59 was associated with the largest gains in CV disease-free life years, while quitting smoking was associated with the greatest increase in overall life expectancy.
Cardiovascular (CV) disease affects nearly 7% of the world’s population, and 5 classical risk factors – hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), abnormal body mass index (BMI), and smoking – account for over half of the global burden of CV disease. Understanding how these risk factors impact lifetime estimates of CV disease and death using individual-level data at a global scale is critical to targeting preventative actions worldwide.
On March 30th 2025, results from “Global Effect of Cardiovascular Risk Factors on Lifetime Estimates” were presented at ACC Scientific Sessions 2025 on behalf of The Global Cardiovascular Risk Consortium, with simultaneous publication in the New England Journal of Medicine. The purpose of this study was to determine how the presence, absence, or modification of classic risk factors at midlife affects lifetime estimates of cardiovascular disease and death from any cause worldwide.
This observational analysis pooled data from 2,078,948 individuals across 6 continents and 39 countries. Participants were followed longitudinally. The exposure was the presence or absence of classic risk factors at age 50. Primary outcomes were estimates of lifetime risk of CV disease and death from any cause, with outcomes estimated through age 90 using Weibull models. CV disease included myocardial infarction, unstable angina, coronary revascularization, ischemic or hemorrhagic stroke, CV death, or unclassifiable death. Risk factor changes during midlife (ages 50–59) were also modeled to assess impact on lifetime outcomes.
Overall, they found that even those with no risk factors still had substantial risk for CV disease. Women with no risk factors had a 13% lifetime risk of CV disease and 53% risk of death before age 90; those with all five risk factors had 24% risk of CV disease and 88% risk of death. Men with no risk factors had a 21% lifetime risk of CV disease and 68% risk of death before age 90; with all five risk factors, those risks increased to 38% and 94%, respectively. By avoiding all 5 risk factors by age 50, women gained 13.3 years of CV-disease free life and 14.5 overall life-years. Men gained 10.6 years of CV disease-free life and 11.8 overall life years. Controlling hypertension at ages 55-60 added the most CV disease-free life years, and stopping smoking added the most overall life-years, followed by blood pressure control. There was additive benefits from control of multiple risk factors. The authors also found geographic variability in lifetime risk of cardiovascular disease.
Limitations include heterogeneity of the data sources in terms of representativeness of the underlying population, follow up times, data quality, end-point definitions. Also, the associations cannot have a causal interpretation due to unmeasured confounding.
Professor Christina Magnussen, from The Global Cardiovascular Risk Consortium (GCVRC) Investigators, University Heart and Vascular Center Hamburg, Hamburg, Germany, concluded: “Even among those who had none of the classical risk factors, the lifetime risk for CV disease remained substantial. The absence of five classical risk factors at age 50 was associated with over a decade greater life expectancy than those who had all five risk factors, in both sexes, and modification of arterial hypertension from present to absent during midlife was related to the most additional life-years for freedom from CV disease.” The findings indicate that “preventive strategies are essential even for low-risk individuals, and targeted interventions on specific risk factors in a critical midlife decade may optimize outcomes. Hypertension (and smoking) should be the primary focus in primary prevention.”