Peptic ulcer (PU) and cardiovascular disease (CVD) are significant chronic illnesses, especially among the elderly, due to their comorbidity and combined impact on mortality (1). PU involves the formation of ulcers in the mucosal lining of the digestive tract, particularly in the lower esophagus, stomach, or duodenum, which may extend through the mucosal layer into the underlying submucosal tissues (2). PU affects around 4 million people annually, with a global lifetime prevalence of 5–10%. The incidence varies from 0.3 to 0.9 per thousand individuals annually (3), while around 54,000 hospitalizations annually in the U.S. are linked to PU bleeding (4). In mainland China, precise national PU prevalence is unknown, though a 2007 Shanghai survey with 1,022 participants found gastric ulcers in 6.07% and duodenal ulcers in 13.31% (5). Key risk factors for PU include Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAIDs) use, aging, smoking and alcohol (3). Age increases PU risk and complications (6, 7). Despite treatment options like acid suppressants, H. pylori eradication, lifestyle changes, and NSAIDs management, PU leads to around 10,000 deaths in the United States annually (4). Consequently, PU continues to be a critical health concern, especially for the elderly.

CVD stands as one of the most challenging global public health burdens, encompassing a range of complex pathological conditions resulting from cardiac and circulatory dysfunction. The clinical manifestations of CVD encompass arrhythmias, heart failure, coronary heart disease and stroke (8, 9). Annually, CVD accounts for approximately 17.9 million deaths, and its global incidence has doubled over the past two decades (10), representing one-third of total global mortality (11). In China, CVD remains the primary contributor to both mortality and premature death (12), contributing to 40% of the national mortality rate (13). The burden of CVD is particularly significant among the elderly population (14), often accompanied by comorbidities and risk factors such as obesity, hypertension, diabetes, dyslipidemia, and smoking (15).

Previous studies have demonstrated a multidimensional interaction between PU and CVD, including drug-induced damage, overlapping risk factors, and inflammatory pathway synergy. In patients with CVD, antiplatelet drugs such as aspirin elevate the risk of developing PU. Smoking and advanced age are common risk factors for both PU and CVD. Helicobacter pylori infection, a common cause of PU, is positively correlated with CVD through virulence factors (16), and its eradication reduces CVD risk (17). The pathophysiological mechanisms of both diseases may involve shared pathways of oxidative stress and immune modulation (18, 19). While the relationship between PU and CVD is complex, the precise link between the two and the influence of comorbidities on mortality remains unclear. Some studies suggest that PU increases CVD risk through systemic inflammation and endothelial dysfunction, with a UK Biobank study of 330,751 individuals showing higher CVD incidence among PU patients (19). However, other research indicates that PU may have a protective role or negligible impact on CVD prognosis. A meta-analysis of 230,288 patients found that HP infection slightly increases cardiovascular risk, far less than earlier studies suggested (16). These inconsistencies highlight the need for further research to clarify the interaction between these diseases. This study uses data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database spanning from 2008 to 2018 to explore the relationship between PU and CVD, with a focus on mortality impact and the potential modifying role of demographic and clinical factors.

This study thoroughly explored the relationship between PU and CVD in the elderly population in China. The results indicated that PU does not have a significant impact on overall mortality or the prognosis of CVD patients. Additionally, CVD was found to be a risk factor for the occurrence of PU, while PU was not identified as a significant risk factor for the development of CVD. However, stratified analysis revealed an association between PU and higher mortality risk in older and male populations. These findings suggest that although PU may not be a significant prognostic factor in the general population, it warrants greater attention in high-risk subgroups, highlighting the need for gender-sensitive approaches and age-stratified management strategies for PU.

The study found that PU did not have a significant impact on overall mortality or the prognosis of CVD patients. Research indicates that the burden of PU in China has shown a downward trend (21), primarily due to the nationwide implementation of standardized H. pylori screening and eradication programs. PU patients, having previously experienced ulcers, often become more aware of the risks related to diet and medication, which may explain why PU does not significantly impact overall mortality. Although our study found no significant association between PU and overall mortality in patients with CVD, the potentially fatal nature of PUD should not be overlooked. Acute complications such as bleeding and perforation often carry high short-term mortality. These events may be especially dangerous in CVD patients due to reduced cardiovascular reserve (23), underscoring the need for early recognition and proactive management in high-risk populations.

Furthermore, our study highlights that the impact of PU on mortality varies by sex and age, with males and older adults at a higher risk. This is consistent with a global study on the burden of PU conducted from 1990 to 2009 across 204 countries and regions (23), which revealed that the highest prevalence, mortality, and disability-adjusted life years (DALYs) for PU occurred in the 80–84 and 85+ age groups. In these age groups, the mortality rate increased sharply, likely due to the decline in gastrointestinal mucosal barrier function and impaired repair capacity in elderly individuals, as well as the increased use of NSAIDs due to comorbid chronic conditions (24). Furthermore, our study found that the mortality risk associated with PU is higher in men. This may be due to the protective effect of estrogen on the gastrointestinal mucosa, which promotes increased bicarbonate secretion and enhances phospholipid levels (25). Additionally, men tend to be more exposed to complex risk factors, such as overeating and excessive alcohol intake, which not only further impact their health and mortality but also reflect difficult-to-overcome unhealthy lifestyle habits, particularly under high societal pressure. These factors may contribute to the higher mortality observed in male PU patients.

As a risk factor for PU, CVD may be primarily associated with the widespread use of NSAIDs and antiplatelet drugs in its treatment. NSAIDs decrease prostaglandin synthesis through the inhibition of COX-1/COX-2, resulting in reduced mucosal blood flow, disruption of the mucosal barrier, and impaired epithelial regeneration, while also directly inducing mitochondrial oxidative phosphorylation uncoupling and intestinal cell damage (26, 27). Non-NSAIDs antiplatelet drugs, such as clopidogrel, inhibit platelet-derived growth factor, which hinders ulcer healing (28). Ticagrelor, a commonly used antiplatelet agent, increases bleeding risk via epigenetic mechanisms. GPD2 hypermethylation suppresses ROS production and NF-κB-mediated P2Y12 expression, impairing platelet reactivity and enhancing susceptibility to ticagrelor-associated gastrointestinal bleeding (32). Additionally, impaired neural regulation between the central nervous system and the gastrointestinal tract in patients with cerebral infarction, including stress responses, parasympathetic excitation, and noradrenergic activation, may contribute to mucosal damage and increase the risk of gastrointestinal bleeding (22).

In this study, PU was not found to be a major determinant in the onset of CVD. PU is often associated with CVD through factors such as H. pylori infection, proton pump inhibitors (PPIs) use, smoking, and other harmful lifestyle habits, Certain studies have indicated that H. pylori infection may facilitate the development of atherosclerotic plaques, thereby increasing the risk of CVD (31), while PPIs may increase CVD risk through mechanisms like cellular damage, adverse drug interactions, and disruptions in metabolic processes (26). However, these studies tend to have small sample sizes and limited impact, so their findings may not be broadly applicable. A large-scale study with 23,000 participants and a median follow-up of 6.3 years found that the effect of H. pylori on CVD risk was minimal (27). Additionally, a meta-analysis showed that while PPIs use reduced the risk of gastrointestinal events, it did not significantly increase major cardiovascular adverse events, including cardiovascular-related deaths, all-cause mortality, or nonfatal myocardial infarctions (32). These studies support our finding that PU is not a significant risk factor for CVD, aligning with the results of our research. Furthermore, most existing studies have focused on the role of mediators such as H. pylori and PPIs in the relationship between PU and CVD, with fewer directly examining the connection between PU and CVD itself. This opens up new avenues for future research.

This study boasts several key strengths, such as the inclusion of a large, well-defined cohort derived from the CLHLS, complemented by longitudinal follow-up data extending over a decade. We employed robust multivariable adjustment models and stratified analysis methods, which enhanced the reliability of our findings. The non-significant interaction between PU and CVD (p = 0.28) suggests that their respective effects on mortality are likely independent rather than synergistic. However, this result may be partly attributed to the limited number of participants with both conditions, which reduced the statistical power to detect interaction effects. These insights reinforce the importance of early detection and preventive strategies in high-risk populations and support our recommendation for age-stratified and gender-sensitive management approaches. Our findings emphasize the clinical need for gastrointestinal risk assessment in elderly CVD patients. Targeted prevention and management strategies, especially in older males, may help reduce adverse outcomes and improve clinical outcomes in patients with coexisting cardiovascular and gastrointestinal conditions.

Nonetheless, this study has several limitations. First, it included participants aged 65–79, which may limit the applicability of the findings to older individuals with different risk profiles and health outcomes. Due to lower adherence to endoscopic screening in older age groups, the prevalence of PU in this population may be underestimated. Moreover, the diagnosis of PU was based on self-reported data without endoscopic confirmation, potentially resulting in misclassification. This may lead to under diagnosis or over-reporting, affecting prevalence estimates and outcome associations. In addition, the database lacked information on ulcer severity, such as Forrest classification, and lesion location, limiting risk stratification. Although acute PU complications such as bleeding and perforation are associated with high short-term mortality (33), detailed clinical data were unavailable. In a large study of 42,046 patients, 80.25% had ulcer-related complications, with bleeding and perforation mortality rates of 2.6 and 5.96% (34). It also did not contain data on concomitant medication use, such as NSAIDs or PPI therapy, which precluded assessment of drug-related ulcer risk and limited interpretation of relevant mechanisms. Furthermore, the cohort, while representative of older adults in China, may not be generalizable to other populations with differing ethnicities, healthcare access, or risk profiles. Finally, the conservative diagnostic criteria and handling of missing data enhanced internal validity but may have reduced sensitivity to detect modest associations. Future research should expand age coverage, incorporate more precise diagnostic tools, and further investigate sex- and age-specific mechanisms to improve risk prediction and guide individualized interventions in elderly PU patients.

This study among an elderly population demonstrates that PU does not significantly affect overall mortality or the prognosis of patients with CVD. While CVD was identified as a risk factor for PU, PU did not notably increase CVD risk. Nonetheless, older adults with PU remain at elevated risk of mortality, emphasizing the importance of early recognition and proactive management. These findings underscore the clinical need for integrated cardiovascular–gastrointestinal risk assessment, particularly in elderly and male patients. Future research should explore underlying mechanisms and long-term outcomes, and develop more refined, stratified intervention strategies to improve care for this vulnerable population.