For decades, doctors have judged blood pressure risk by a single, deceptively simple number: the average. But a sweeping new study drawing on nearly 190,000 adults from the UK Biobank suggests that the story may lie not in how high blood pressure runs, but in how wildly it swings from one clinic visit to the next. Researchers report that visit-to-visit variability in systolic blood pressure—the top number in a blood pressure reading—is independently associated with a substantially elevated risk of developing an abdominal aortic aneurysm, a silent bulge in the body’s largest artery that can rupture with often fatal consequences. The findings, published in the European Journal of Epidemiology, add a dynamic dimension to cardiovascular risk assessment that static averages have long missed.

Abdominal aortic aneurysms, or AAAs, develop when the wall of the aorta in the abdomen weakens and balloons outward. They are notoriously stealthy: most people carry one without symptoms until it grows large enough to press on surrounding tissue or, catastrophically, ruptures. Ruptured AAAs carry high mortality, and even in settings with rapid surgical response, survival is far from guaranteed. Because the condition is usually asymptomatic in its early stages, identifying modifiable risk factors is one of the most important public health levers available. Elevated mean blood pressure has long been recognized as a contributor, but the new study argues that traditional measures inadequately capture the true hemodynamic stress imposed on the arterial wall.

The research team, led by Ziqin Cao and Qiong Huang of Central South University’s Second Xiangya Hospital together with colleagues, analyzed data from 189,770 UK Biobank participants who had at least three systolic blood pressure measurements linked to primary care records. Rather than relying on a single snapshot, the investigators calculated variability across repeated visits, using multiple statistical metrics to quantify how much each person’s readings fluctuated over time. They then followed the cohort for a median of 10.7 years, during which 1,036 participants developed an incident abdominal aortic aneurysm. Cox proportional hazards models allowed the team to estimate aneurysm risk while adjusting for a battery of cardiovascular risk factors and, crucially, for mean systolic blood pressure itself.

The results were striking in their consistency. Across every variability metric examined, higher systolic blood pressure variability was associated with increased aneurysm risk, with trend tests reaching statistical significance at P values of 0.003 or lower. When the researchers compared participants in the highest tertile of variability with those in the lowest, they found a 33 to 54 percent increase in risk, depending on the metric used. Dose-response analyses suggested the relationship was approximately linear, meaning that each incremental increase in fluctuation corresponded to a proportionally greater hazard, without any apparent threshold effect. Sensitivity analyses designed to probe the robustness of the association—including adjustments for antihypertensive medication use and other potential confounders—left the core finding intact.

Perhaps the most clinically provocative result concerns people whose average blood pressure looks reassuringly normal. Even among participants whose mean systolic pressure remained below 130 mmHg—a level generally considered well controlled under contemporary guidelines—high visit-to-visit variability still conferred elevated aneurysm risk. This suggests that a patient can tick the box for adequate blood pressure control on paper while still experiencing mechanical stresses that may insidiously damage the aortic wall. The biological rationale is plausible: the aorta is an elastic conduit that expands and recoils with every heartbeat, and repeated cycles of stretch and relaxation at varying amplitudes may accelerate degradation of elastin and collagen in the vessel wall, promote inflammation, and foster the endothelial dysfunction that experimental studies have implicated in aneurysm formation.

The study went beyond epidemiology by layering on genomic and proteomic profiling, an approach that reflects a broader movement in cardiovascular research toward multi-omics risk stratification. Using polygenic risk scores, the team stratified participants by inherited susceptibility to abdominal aortic aneurysm. The interaction was dramatic: individuals with both high blood pressure variability and high genetic risk faced more than a two-fold increase in aneurysm incidence, with hazard ratios ranging from 2.07 to 2.28 and P values below 0.001. In other words, genes and hemodynamic turbulence did not merely add together—they appeared to amplify one another, echoing a growing literature showing that genetic predisposition can accentuate the harm of modifiable exposures across conditions from fatty liver disease to obesity-related illness.

To probe the molecular pathways that might connect fluctuating pressure to aneurysm development, the researchers turned to proteomics, measuring circulating proteins and conducting exploratory analyses of indirect effects. Ten proteins showed statistically significant indirect associations after controlling the false discovery rate, with descriptive coefficient-attenuation estimates ranging from 6.7 to 30.4 percent. The authors are careful to frame these findings appropriately: the protein-specific estimates are non-additive and do not establish causal mediation. Still, the identification of candidate circulating proteins offers a molecular bridge between a hemodynamic exposure and a structural vascular disease, and it aligns with recent proteome-wide studies that have nominated inflammatory and lipid-related pathways as central to aneurysm biology.

The study’s strengths are considerable. Its prospective design means blood pressure variability was measured before aneurysms developed, reducing the risk of reverse causation. The sheer scale of the UK Biobank, combined with linked primary care records, provided the repeated measurements needed to compute variability reliably—something smaller cohorts cannot do. The adjustment for mean systolic pressure is particularly important, because variability and average pressure are correlated, and an apparent variability effect could otherwise simply reflect underlying hypertension. By demonstrating that the association persists after accounting for the average, the analysis makes a credible case that variability carries independent information.

Yet the authors and the data itself impose clear limits on interpretation. An observational cohort, however large and well adjusted, cannot prove that smoothing out blood pressure swings would prevent aneurysms. Residual confounding by factors such as medication adherence, measurement error, or underlying illness remains possible, and the exploratory proteomic findings require replication. The researchers explicitly state that their results support systolic blood pressure variability as a potential risk marker and warrant external validation in other populations, but do not establish that reducing variability would avert the disease. That caveat matters, because variability can reflect many things—from genuine hemodynamic lability to inconsistent measurement conditions or irregular medication taking—and interventions targeting it have not been tested for aneurysm prevention.

Even with those qualifications, the study is likely to resonate widely, both in clinics and among the public. It reframes a familiar vital sign as a dynamic signal, hinting that the quiet patient with borderline readings and erratic follow-up measurements may be anything but low risk. It dovetails with prior work linking blood pressure variability to cardiovascular events, chronic kidney disease, dementia, and death, and it complements emerging efforts to build polygenic risk scores and proteomic panels into aneurysm screening programs. For now, the practical message is one of heightened vigilance rather than new prescriptions: clinicians may want to pay closer attention to the consistency of blood pressure control in genetically susceptible patients, and researchers now have a concrete, testable hypothesis about how mechanical stress and inherited vulnerability conspire to weaken the aorta. As with many advances in precision medicine, the swing of the pendulum—in this case, quite literally the swing of a blood pressure reading—may prove as informative as its resting position.

Subject of Research: The association between visit-to-visit systolic blood pressure variability and abdominal aortic aneurysm risk, examined with genomic and proteomic profiling.

Article Title: Systolic blood pressure variability as a risk factor for abdominal aortic aneurysm: a prospective cohort study with genomic and proteomic profiling

Article References: Cao, Z., Huang, Q., Zeng, Y., Nan, W., Li, Y., He, B., Chai, X., & Peng, Z. (2026). Systolic blood pressure variability as a risk factor for abdominal aortic aneurysm: a prospective cohort study with genomic and proteomic profiling. European Journal of Epidemiology. https://doi.org/10.1007/s10654-026-01459-2

Image Credits: AI Generated

DOI: 10.1007/s10654-026-01459-2

Keywords: blood pressure variability, abdominal aortic aneurysm, hypertension, UK Biobank, polygenic risk score, proteomics, cardiovascular disease, aortic wall, risk factors, epidemiology, genetic susceptibility, aneurysm prevention

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