Editorial
Prevention is rarely about a single decision made at a single point in time. The risks that shape health accumulate over years and decades, but the opportunities to modify them also change. What matters in early adulthood may be reducing long-term exposure to cardiovascular risk. During pregnancy, prevention can extend to the next generation. In midlife, it may mean finding disease before symptoms appear. Later on, the goal may shift toward preserving physical function, avoiding unnecessary treatment, and making sure preventive care still reflects an individual's priorities and likely benefit.
This life-course perspective is increasingly important as populations live longer and chronic diseases emerge from combinations of cumulative exposure, behavior, biology, and social context. Living longer also means having more time for these exposures to accumulate. I have come to think of age not only as a risk factor in itself, but also as a marker of the time over which risks (and protections) have had the opportunity to act. Two people can reach the same chronological age through very different trajectories, shaped by decades of exposure, health, and resilience. From this perspective, the risk we observe later in life reflects not only the present, but also the path that led there. A life-course approach to prevention therefore asks us to consider how risk develops over time, what remains modifiable, and what matters most at each stage of life.
This issue of Longevity Brief looks at prevention as a moving target, exploring how timing, reach, and context shape prevention across the life course. The studies selected this month range from the global burden of elevated LDL cholesterol to statin discontinuation in later life, physical function, cancer screening, and maternal vaccination. Together, they illustrate how prevention can mean reducing cumulative exposure decades before disease appears, protecting someone before birth, making sure an effective screening program is actually completed, preserving function in older age, or reconsidering whether a treatment that once made sense still offers meaningful benefit. These studies suggest a broader principle: good prevention is not simply about doing more, or even always about starting earlier. It is about matching the intervention to the stage of life, the level of risk, and the outcomes that matter most at that moment.
The question, then, is not only what can we prevent? It is also when is the right time to act, for whom, and with what goal?
Lead study
When progress is not enough: the growing global burden of LDL cholesterol
Featured paper: Global Burden of Elevated LDL-C: Findings From the Global Burden of Disease Study 2023
The question
How much disease and premature mortality worldwide can be attributed to elevated LDL cholesterol, and how has that burden changed over the past three decades?
What the study found
The GBD 2023 LDL Cholesterol Collaborators estimated the burden attributable to elevated LDL-C among adults aged 25 years or older across 204 countries and territories.
In 2023, elevated LDL-C accounted for an estimated 3.6 million deaths, representing 6.0% of all deaths globally, and 90.7 million disability-adjusted life years, or DALYs. Ischemic heart disease and ischemic stroke accounted for the attributable cardiovascular burden.
There has been substantial progress. Since 1990, age-standardized mortality attributable to elevated LDL-C declined by 45.6%, while age-standardized DALY rates declined by 39.5%.
But the absolute burden moved in the opposite direction. The total number of LDL-C-attributable DALYs increased by 38.5%, largely as a consequence of population growth and population aging. One-third of the global burden in 2023 occurred in China and India, while the distribution of risk increasingly shifted toward countries at middle levels of sociodemographic development.
Why it matters
The distinction between rates and absolute numbers is central to population prevention.
Cardiovascular prevention has become more effective in many parts of the world, yet demographic change means that more people are living long enough to accumulate exposure to atherogenic cholesterol and experience its consequences.
LDL-C is particularly relevant to a life-course perspective because cardiovascular risk reflects not simply a measurement taken today, but the magnitude and duration of exposure over time. Prevention therefore cannot begin only when short-term risk becomes high.
At a population level, the study also highlights a second challenge: scientific advances do not automatically translate into equitable prevention. Measurement, diagnosis, treatment access, and long-term control remain unevenly distributed worldwide.
Keep in mind
GBD estimates combine multiple data sources and statistical models. They are designed to quantify population burden, not to determine an individual person's cardiovascular risk.
Research worth knowing
In later life, prevention may require reconsidering what should continue
Featured paper: Discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older (SAGA/SITE): a multicentre, open-label, pragmatic, non-inferiority randomised trial
The question
Among adults aged 75 years or older taking a statin for primary prevention, does stopping treatment result in higher mortality than continuing it?
What the study found
The pragmatic SAGA/SITE trial enrolled 1,180 adults aged 75 years or older who had used statins for at least one year, had no history of atherosclerotic cardiovascular disease, and were receiving treatment exclusively for primary prevention.
In the primary analysis, 1,160 participants were included. Median age was 80 years, 66.8% were women, 29.5% had diabetes, and 77.2% had hypertension.
After 36 months, 7.9% of participants assigned to continue statins and 7.2% of those assigned to discontinue them had died. The absolute difference was -0.68% (95% CI -3.95 to 2.60), meeting the prespecified criterion for non-inferiority of discontinuation for all-cause mortality.
Adverse event rates were also similar between groups.
Why it matters
This study sits almost deliberately in tension with the global LDL-C data.
Preventing cumulative exposure earlier in life remains important. Yet prevention in an 80-year-old already taking medication raises additional questions about competing risks, time to benefit, treatment burden, multimorbidity, and personal priorities.
A life-course approach should therefore not mean applying one preventive strategy indefinitely. It means periodically asking whether the balance of benefit and burden has changed.
Keep in mind
The primary endpoint was all-cause mortality over three years. The trial was not designed to prove that statin discontinuation is preferable for every older adult, and decisions remain individualized.
Preserving physical function: lifestyle did the work, metformin did not add more
Featured paper: Metformin added to lifestyle intervention for physical function in older adults with obesity (DEMFOS trial): a randomised controlled trial
The question
Can metformin enhance the improvement in physical function achieved through intensive lifestyle intervention in older adults with obesity?
What the study found
The DEMFOS trial randomized 114 adults aged 65 to 85 years with obesity to intensive lifestyle intervention plus placebo, intensive lifestyle intervention plus metformin, or healthy lifestyle education plus metformin.
The primary outcome was change at six months in the modified Physical Performance Test, providing an explicit measure of functional performance rather than relying only on body weight or metabolic biomarkers.
Participants receiving intensive lifestyle intervention plus metformin improved by 2.5 points more than those receiving healthy lifestyle education plus metformin.
However, adding metformin to intensive lifestyle intervention produced essentially no additional functional benefit compared with intensive lifestyle intervention plus placebo: mean difference 0.1 points (95% CI -1.2 to 1.4).
Why it matters
Weight management in later life should not be judged solely by kilograms lost.
For healthy aging, an equally important outcome is whether an intervention preserves or improves the ability to perform physical tasks. In this trial, structured diet and exercise improved functional performance, while adding another pharmacological intervention did not enhance that effect.
It is a useful reminder that prevention aimed at longer lives should also protect the capacities needed to live them well.
Keep in mind
The study was relatively small and 89% of participants were men, which limits how broadly its findings can be generalized.
Effective screening still depends on getting people back through the door
Featured paper: Health Communication and Stepped Reminders Interventions for Lung Cancer Screening: A Randomized Clinical Trial
The question
Can targeted communication and health-system reminders improve adherence to annual lung cancer screening?
What the study found
A pragmatic randomized trial at Kaiser Permanente Washington included 1,837 adults who had already completed an initial lung cancer screening examination with normal findings.
Participants received usual care, additional health communication, a stepped-reminder intervention, or both.
Providing additional educational communication did not improve annual screening adherence. The stepped-reminder strategy, which prompted primary care physicians to order screening and contacted patients to schedule low-dose CT, did.
Screening adherence was 75.5% among participants receiving stepped reminders compared with 47.4% among those who did not, corresponding to a relative risk of 1.59. The effect was particularly large among participants who were still using tobacco.
Why it matters
Developing an effective preventive intervention is only part of the job.
Screening programs fail when eligible people are never screened, but also when follow-up becomes fragmented after the first examination. This trial shows how relatively simple health-system design can substantially alter whether evidence-based prevention actually reaches patients.
Prevention is therefore not only about identifying the right test. It is also about building systems in which the test happens at the right time.
Keep in mind
Participants were already engaged in an integrated health system and had completed an initial screening examination, so implementation may look different in less integrated settings.
One vaccination can protect across generations
Featured paper: Vertical Vaccination Against Infant Influenza Hospitalization in a Tropical Setting
The question
Does influenza vaccination during pregnancy reduce the risk of influenza hospitalization during an infant's first six months of life in a setting with year-round viral transmission?
What the study found
Using linked national data from Singapore, investigators studied 221,185 infants born between 2017 and 2023. Just over one-quarter were born to mothers who had received influenza vaccination during pregnancy.
Infants born to vaccinated mothers had a substantially lower risk of influenza hospitalization during their first six months of life, with an adjusted hazard ratio of 0.59.
This corresponded to an estimated 41% vaccine effectiveness against hospitalization (95% CI 23% to 55%). Protection was observed regardless of whether vaccination occurred during the first, second, or third trimester.
Why it matters
Few examples illustrate life-course prevention as clearly.
Infants younger than six months cannot yet receive influenza vaccination themselves. Maternal immunization allows prevention to begin before birth, transferring protection across generations during a period of particular vulnerability.
The study also broadens the usual image of prevention as something directed exclusively at the individual receiving an intervention. Sometimes protecting one person means intervening in another.
Keep in mind
This was an observational cohort rather than a randomized trial, although the use of linked nationwide registries allowed adjustment for a wide range of measured characteristics.
Beyond the headlines
The target of prevention moves with age
Featured paper: Modifiable Risk Factors for Mortality Across Life Course: A Pooled Population-Based Cohort Study
Most preventive frameworks identify lists of modifiable risk factors. Chen and colleagues asked a different question: does the relative importance of those risks remain the same throughout life?
The investigators pooled three Chinese population cohorts comprising approximately 61,000 participants, with age groups ranging from 30 to 49 years through 100 years and older. Eleven potentially modifiable metabolic, behavioral, and social factors were examined in relation to all-cause mortality.
The overall accumulation of modifiable risks remained associated with mortality across the life course. But the composition of that risk changed.
Metabolic factors showed progressively weaker associations at more advanced ages. Hypertension, for example, accounted for a substantial proportion of mortality in earlier age groups but far less among the longest-lived participants.
By contrast, low educational attainment showed an increasing relative contribution with advancing age, while physical inactivity remained relevant across widely separated stages of life, including among centenarians.
The study should not be read as evidence that hypertension somehow ceases to matter after a certain birthday. Survivor selection, competing risks, and differences between age cohorts complicate that interpretation.
Its more important contribution is conceptual: prevention is dynamic.
The exposures that deserve the greatest attention at 40 may not have the same relative importance at 80 or 100. A life-course model of prevention should therefore adapt priorities as physiology, accumulated exposures, social context, competing risks, and individual goals change.
The objective stays remarkably stable: preserve health and function for as long as possible. The route to that objective does not.
What I'm watching
Vaccination is becoming part of cardiovascular prevention
In August, the American College of Cardiology published its updated 2026 Concise Clinical Guidance on Adult Immunizations as Part of Cardiovascular Care.
The guidance integrates influenza, pneumococcal, COVID-19, and RSV vaccination into cardiovascular care, while also highlighting emerging evidence linking zoster vaccination to cardiovascular protection. It reflects growing evidence that respiratory infections can precipitate myocardial infarction, heart failure decompensation, hospitalization, and other cardiovascular events, and that vaccination can reduce severe infection and some of its downstream consequences.
Perhaps more importantly, the guidance treats vaccination as something cardiovascular clinicians should actively assess rather than leave entirely to another part of the health system.
That shift is worth watching.
As prevention becomes more integrated, the boundary between infectious disease prevention and chronic disease prevention may become increasingly artificial.
Closing thought
Good prevention is not simply more prevention.
It is the right intervention, delivered at the right moment, to the right population, with outcomes that remain meaningful at that stage of life.
Sometimes that means lowering exposure decades before disease appears. Sometimes it means making sure an effective screening program actually reaches people. Sometimes it means preserving physical function. And sometimes it means reconsidering an intervention that made sense earlier but may no longer offer the same balance of benefit.
Thinking across the life course makes prevention more complex.
It also makes it more human.
References
- GBD 2023 LDL Cholesterol Collaborators. Global Burden of Elevated LDL-C: Findings From the Global Burden of Disease Study 2023. JAMA. Published online July 29, 2026.
- Bonnet F, et al. Discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older (SAGA/SITE): a multicentre, open-label, pragmatic, non-inferiority randomised trial. The Lancet Healthy Longevity. 2026;7(7):100884.
- Duremdes Nava ML, Viola V, Aguilar M, et al. Metformin added to lifestyle intervention for physical function in older adults with obesity (DEMFOS trial): a randomised controlled trial. The Lancet Healthy Longevity. Published online July 30, 2026.
- Wernli KJ, Anderson ML, Palazzo L, et al. Health Communication and Stepped Reminders Interventions for Lung Cancer Screening: A Randomized Clinical Trial. JAMA Internal Medicine. Published online August 10, 2026.
- Wee LE, Goh NS, Ho RW, et al. Vertical Vaccination Against Infant Influenza Hospitalization in a Tropical Setting. JAMA Network Open. 2026;9(8):e2628389.
- Chen S, Wang S, He B, et al. Modifiable Risk Factors for Mortality Across Life Course: A Pooled Population-Based Cohort Study. The Journals of Gerontology: Series A. Published online August 17, 2026.
- Heidenreich PA, Bhatt A, Nazir NT, Schaffner W, Vardeny O. Adult Immunizations as Part of Cardiovascular Care: 2026 ACC Concise Clinical Guidance: A Report of the American College of Cardiology Solution Set Oversight Committee. Journal of the American College of Cardiology. Published online August 5, 2026.