Aneurysms, particularly intracranial and aortic aneurysms, represent a significant health concern due to their potential for rupture, which can lead to life-threatening complications.

While many individuals remain unaware of their presence until an emergency arises, understanding the risk factors that contribute to aneurysm formation and rupture is crucial for early detection and prevention.

Key Risk Factors: The Interplay of Genetics, Lifestyle, and Clinical Conditions

Recent research underscores that aneurysm risk is multi-factorial, involving a complex interaction of genetic predisposition, environmental influences, and clinical comorbidities. Hypertension consistently emerge as the most significant modifiable risk factors.

A family history of aneurysms also markedly increases risk, suggesting a hereditary component that may involve connective tissue disorders or genetic mutations affecting vascular structure.

Dr. Babak S. Jahromi, MD, PhD, Co-director, Cerebrovascular & Skull-base Surgery Programs, explains "Genetic predisposition sets the stage for aneurysm formation, but modifiable factors—especially hypertension, and other lifestyle choices—are what frequently tip the balance toward growth or rupture."

Demographic and Biochemical Predictors: Beyond the Traditional

Emerging studies reveal demographic nuances: female and older age correlate with higher rupture risk, possibly due to hormonal influences and vascular aging. Intriguingly, younger patients tend to have a reduced rupture risk, highlighting the dynamic nature of aneurysm progression.

Biochemical markers such as elevated neutrophil counts, lactate dehydrogenase (LDH), D-dimer, and glucose levels have been identified as predictors of rupture risk. These markers reflect underlying inflammation, coagulation abnormalities, and metabolic stress that compromise vessel wall stability. Lower hematocrit and fibrinogen levels also associate with increased rupture likelihood, suggesting that blood composition influences aneurysm vulnerability.

Anatomical and Morphological Considerations

Aneurysm size, location, and shape critically influence rupture risk. Larger aneurysms, particularly those exceeding 11 millimeters, and those located in the posterior circulation of the brain, carry a higher risk. Irregular or multilobulated aneurysm shapes indicate unstable walls more prone to rupture.

Moreover, the presence of multiple aneurysms amplifies risk, especially if a prior rupture has occurred. These factors necessitate vigilant monitoring and individualized risk stratification.

The Role of Comorbidities and Lifestyle Factors

Diabetes mellitus and hyperlipidemia have complex associations with aneurysm risk. While some epidemiological data suggest diabetes might confer a paradoxical protective effect against subarachnoid hemorrhage, other studies indicate an increased risk of aneurysm growth in diabetic patients, possibly due to frequent imaging and early detection.

Toward Personalized Risk Assessment and Prevention

The heterogeneity of aneurysm pathogenesis calls for personalized risk assessment frameworks. Integrating demographic data, genetic profiles, biochemical markers, and imaging findings enables clinicians to identify high-risk individuals and tailor preventive strategies effectively.

John A. Elefteriades, MD emphasizes, "The marked heterogeneity of aneurysm pathogenesis demands that we move beyond one-size-fits-all criteria. By integrating high-resolution imaging, genomic data, biomechanical modeling, and patient-specific biomarkers, we can create personalized risk calculators that shift our entire paradigm—from reacting after rupture to preventing rupture in the first place."

Aneurysm risk is shaped by a constellation of factors—modifiable and non-modifiable that interact in complex ways. Awareness of these determinants empowers patients and healthcare providers to engage in early detection, lifestyle modification, and appropriate surveillance, ultimately reducing the devastating impact of aneurysm rupture.