Long-term mortality and cause-specific death after non-cardiac chest pain: a multicentre cohort study of 160,245 patients in China
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Background
Non-cardiac chest pain (NCCP) is commonly regarded as a low-risk condition. However, long-term mortality, cause-specific death, and high-risk subgroup characteristics remain poorly defined.
Methods
In this multicentre registry-linked cohort study, we linked the Chest Pain Center Registry from 101 hospitals in Hunan, China, with the Mortality and Cause of Death Registry. Adults diagnosed with NCCP from Jan 1, 2017, to Dec 31, 2021, were included. We assessed 3-year all-cause, cardiovascular, and non-cardiovascular mortality using Cox, restricted cubic spline, and Fine-Gray models.
Findings
Among 160,245 patients, 4674 deaths occurred within 3 years (2.9%). Mortality increased sharply after 60.5 years. Age ≥ 60.5 years (adjusted hazard ratio [aHR] 7.49 [95% CI 6.89-8.14]), rural residence (time-varying aHR 1.46 [1.35-1.57] in year 1 and 1.66 [1.46-1.89] in years 1-3), and male sex (aHR 1.47 [1.38-1.57]) independently predicted death. Three-year mortality ranged from 0.3% in younger urban women to 8.4% in older rural men. Cardiovascular diseases accounted for 56.4% of deaths among older patients, whereas other non-cardiovascular causes (22.8%) and malignancy (20.8%) were the largest categories among younger decedents.
Interpretation
NCCP is not uniformly benign. Age, rural residence, and sex identify patients who could benefit from risk-stratified follow-up, with cardiovascular prevention prioritised for older rural men and broader non-cardiovascular assessment considered for younger patients.
Research in context
Evidence before this study
We searched PubMed from database inception to June 4, 2026, without date restrictions or language filters, using combinations of “non-cardiac chest pain”, “noncardiac chest pain”, “non-specific chest pain”, “nonspecific chest pain”, and “undiagnosed chest pain” with “prognosis”, “mortality”, “long-term”, “cause-specific”, and “cardiovascular mortality”. We considered systematic reviews and cohort studies reporting prognosis, mortality, cardiovascular outcomes, recurrent health-care use, or cause-specific outcomes after NCCP, non-specific chest pain, or undiagnosed chest pain. Previous evidence, including cohort studies with several years of follow-up, suggests that patients with NCCP or related chest pain diagnoses are not a homogeneous low-risk group. However, definitions, clinical settings, and outcomes have varied substantially, and cause-specific mortality has not been consistently reported. In our search, we did not identify large multicentre registry-linked studies examining long-term cause-specific mortality after NCCP or how age, sex, and urban-rural context shape risk after chest pain centre discharge.
Added value of this study
This multicentre registry-linked cohort included 160,245 patients with NCCP from 101 chest pain centres in Hunan, China, linked to a mortality and cause-of-death registry. The study provides 3-year estimates of all-cause, cardiovascular, and non-cardiovascular mortality, characterises cause-of-death composition, and uses competing-risk methods to separate cardiovascular from non-cardiovascular death. It also shows that simple variables available at presentation, age, sex, and residence, identify a steep mortality gradient, with older rural men having the highest absolute risk.
Implications of all the available evidence
The available evidence and our findings support reframing NCCP as a potential entry point for risk-stratified follow-up rather than as reassurance alone. Age, sex, and residence could help chest pain services and primary care systems identify patients who need closer post-discharge surveillance. The urban-rural gradient also points to continuity of care and access to cardiovascular prevention as public health priorities after chest pain evaluation. Follow-up strategies should be aligned with competing risks: cardiovascular prevention may be most relevant for older patients, whereas broader assessment of non-cardiovascular conditions may be appropriate for younger patients. Future studies should test whether targeted follow-up pathways can improve long-term outcomes after NCCP.
