Absence and Midlife Reversal of Cardiovascular Risk Factors Strongly Predict Long-Term Survival: NEJM Global Analysis

Absence of five key cardiovascular risk factors (hypertension, hyperlipidemia, abnormal body mass index, diabetes mellitus, and tobacco use) at age 50 is associated with over a decade of increased life expectancy, with midlife control of blood pressure and smoking offering the greatest gains, a global study finds.

In what may emerge as a touchstone reference for preventive cardiology, the Global Cardiovascular Risk Consortium (GCVRC) has published a comprehensive analysis in The New England Journal of Medicine (March 2025), examining how five modifiable cardiovascular risk factors influence lifetime risk of cardiovascular disease (CVD) and all-cause mortality—across 133 cohorts spanning six continents and over 2.08 million individuals.

While well-established risk factors—arterial hypertension, hyperlipidemia, abnormal body mass index (BMI), diabetes mellitus, and tobacco use—are already known for their cumulative burden, this study provides robust global evidence by quantifying the lifetime impact of both risk-factor burden and risk modification in midlife. For clinicians, this enables more informed counseling and supports timely intervention strategies during the fifth and sixth decades of life.

Risk-Free at 50: A Decade’s Worth of Life

At 50 years of age, individuals without any of the five risk factors had substantially lower lifetime risks of CVD—13% in women and 21% in men—compared to those with all five risk factors (24% and 38%, respectively). The corresponding increase in CVD-free life-years was 13.3 years in women and 10.6 in men. Life-years free of death were even greater: 14.5 years in women and 11.8 in men.

These figures represent a considerable extension of healthy life span, with implications for the prevention of myocardial infarction, stroke, and other cardiovascular events.

Smoking and Hypertension: The Biggest Levers

When individual factors were analyzed, smoking cessation was associated with the greatest increase in years free of death—5.6 years in women and 5.1 years in men. Hypertension control conferred the most additional CVD-free life-years when modified during midlife—4.7 years in women and 4.2 in men.

This distinction is clinically important: while midlife control of hypertension yielded the greatest increase in cardiovascular disease–free life-years, smoking cessation was associated with the most additional years free from death, according to the study findings.

Lipids and BMI: Modest but Variable Effects

The benefits of controlling hyperlipidemia and BMI were less consistent. Aiming for non-HDL cholesterol <130 mg/dL showed neutral or negative associations with life expectancy unless regional variation was accounted for. Similarly, BMI in the 20–25 range showed modest benefit, which increased when regional standard-deviation scores were applied. These findings highlight the importance of context-sensitive targets rather than uniform cutoffs.

Risk Modification in Midlife: Still Worthwhile

Importantly, the study evaluated participants who had all five risk factors between ages 50 and 55 and then modified them by age 60. Results showed that controlling hypertension during this interval led to 2.4 additional CVD-free life-years in women and 1.2 in men, while smoking cessation conferred 2.1 and 2.4 additional years free of death, respectively.

These results reinforce that meaningful benefits from intervention are still possible in midlife—even after earlier exposure to multiple risk factors.

Toward Lifetime-Based Risk Assessment

Unlike conventional 10-year risk estimates, this analysis projects outcomes over the full lifespan, offering a longer-term view of benefit. By doing so, it enables a preventive narrative that focuses not just on avoiding near-term events but on gaining healthy years of life.

Reference: Magnussen C, Ojeda FM, Blankenberg S, et al; Global Cardiovascular Risk Consortium. Global effect of cardiovascular risk factors on lifetime estimates of cardiovascular disease and death. N Engl J Med. 2025;390(13). doi:10.1056/NEJMoa2415879