Long-term cardiovascular outcomes and risk factors in adult sepsis survivors: a systematic review and meta-analysis

doi:10.5847/wjem.j.1920-8642.2025.098

Abstract

Abstract:

BACKGROUND: Sepsis may increase the risk of long-term cardiovascular outcomes. This study aims to investigate association between sepsis survivorship and cardiovascular outcomes and to identify risk factors.

METHODS: We conducted a comprehensive systematic search of MEDLINE, EMBASE, the Cochrane Library, Wanfang, and CNKI from database inception through May 2025, without language restrictions. The primary outcome was a composite of myocardial infarction, stroke, congestive heart failure, or cardiovascular death. To evaluate the association between sepsis survivors and cardiovascular outcomes, we calculated cumulative incidence rates and hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs).

RESULTS: Twenty-five observational studies comprising 7,525,271 participants were included. The pooled cumulative incidence of major cardiovascular events was 9.0% (95% CI: 6.1%-11.9%), myocardial infarction 2.4% (95% CI: 1.6%-3.1%), stroke 4.9% (95% CI: 3.8%-6.1%), and congestive heart failure 8.6% (95% CI: 4.6%-12.6%). Compared with non-sepsis controls, sepsis survivors had a significantly higher risk of major cardiovascular events (HR: 1.54; 95% CI: 1.32-1.79), myocardial infarction (HR: 1.41; 95% CI: 1.29-1.54), stroke (HR: 1.45; 95% CI: 1.32-1.60), and congestive heart failure (HR: 1.51; 95% CI: 1.46-1.56). Risk factors associated with increased cardiovascular events in sepsis survivors included age ≤ 45 years, male, hyperlipidemia, and multiple comorbidities.

CONCLUSION: Adult sepsis survivors may face significantly increased risks of long-term cardiovascular outcomes. Both common cardiovascular risk factors and sepsis-related pathophysiological changes contribute to this association.

Key words: Sepsis, Sepsis survivors, Cardiovascular outcomes, Stroke, Risk factors

Zesheng Wu, Fanghui Chen, Chen Xiao, Xue Zhao, Yuansheng Xu, Jinyan Fang, Yinyan Shao. Long-term cardiovascular outcomes and risk factors in adult sepsis survivors: a systematic review and meta-analysis[J]. World Journal of Emergency Medicine, 2025, 16(5): 423-430.

Figures/Tables 3

Table 1.

Characteristics of included studies in this meta-analysis

Study (year)	Study design	Case number	Age, year (SD)	Female (%)	Control subjects	Main confounding adjustment	Follow-up	Outcome
Ishani 2005^[27]	Prospective cohort	2,311	62.5 (15.5)	46.7	Population non-sepsis control group	Age, sex, race, multiple comorbidities	3 years	MI, stroke, CHF, PVD
Lee 2013^[28]	Matched cohort	23,027	55.1 (25.0)	47.3	Population non-sepsis control group	Age, sex, multiple comorbidities	10 years	Stroke
Yende 2014^[29]	Retrospective cohort	1,638,566	77.4 (7.8)	55.8	Population non-sepsis	Age, sex, multiple comorbidities	1 year	CVD, MI, stroke
Walkey 2014^[30]	Retrospective cohort	138,722	80.0	57.5	No control group	No	5 years	Stroke, CHF
Jafarzadeh 2016^[31]	Prospective cohort	47,009	59.0	47.8	Hospitalized non-sepsis control group	Age, sex, race, multiple comorbidities, demographics	5 years	CVD, MI, stroke, TIA
Ou 2016^[32]	Retrospective cohort	204,643	64.7 (17.1)	47.4	Hospitalized non-sepsis control group	Age, sex, multiple comorbidities	6.7 years	MI, stroke, stroke
Wang 2017^[33]	Matched cohort	6,420	67.2 (9.2)	53.7	Population non-sepsis control group	Age, sex, race, multiple comorbidities	10 years	CHD
Boehme 2017^[34]	Case-crossover	50,194	71.7 (14.6)	52.2	Population non-sepsis control group	Age, sex, DM	1 year	Stroke
Shih 2017^[35]	Matched cohort	130,530	71.0 (13.2)	47.4	Hospitalized non-sepsis control group	Age, sex, multiple comorbidities	2.5 years	MI, stroke, CHF
Cheng 2017^[36]	Retrospective cohort	68,324	67.3 (17.4)	47.8	No control group	No	1 year	Stroke
Cheng 2017^[37]	Retrospective cohort	7,419	69.8 (12.2)	46.7	No control group	No	4.6 years	Stroke
Lai 2018 ^[38]	Retrospective cohort	42,316	67.7 (17.6)	40.8	Hospitalized non-sepsis control group	Age, sex, Charlson Score, multiple comorbidities	0.5 year	MI, stroke
De Geer 2018^[39]	Matched cohort	13,669	66.4 (15.5)	44.4	Hospitalized non-sepsis control group	Age, sex, illness severity	2 years	CVD, CHF
Vallabhajosyula 2018^[40]	Retrospective cohort	434	68.0	47.2	No control group	No	2 years	CHF
Gadre 2019^[41]	Retrospective cohort	898,257	66.0 (17.6)	51.8	No control group	No	30 days	CVD, CHF
Shao 2019^[42]	Retrospective cohort	121,947	65.3 (20.3)	49.2	No control group	No	1 year	Stroke
Hsieh 2019^[43]	Prospective cohort	42,316	70.4 (16.6)	40.9	No control group	No	0.5 year	MI, stroke
Wu 2019^[44]	Matched cohort	84,467	74.3 (12.5)	42.4	Hospitalized non-sepsis control group	Age, sex, race, multiple comorbidities	1 year	MI, stroke, CVD, MI, ICH
Sebastian 2019^[45]	Case-crossover	152,356	No	No	No control group	No	1 year	Stroke
Hsiao 2022^[46]	Retrospective cohort	4,323	60.1 (17.5)	47.2	No control group	No	0.5 year	CVD, IHD, stroke
Angriman 2022^[10]	Matched cohort	508,482	68.3 (17.4)	57.5	Population non-sepsis control group	Age, sex, demographics, CVD risk factors, comorbidities	5 years	CVD, MI, stroke
Walkey 2023^[47]	Retrospective cohort	82,748	78.0 (11.0)	47.0	No control group	No	1 year	Stroke, TIA
Jentzer 2023^[11]	Retrospective cohort	2,258,464	68.7 (13.2)	54.2	Hospitalized non-sepsis control group	Age, sex, race, CVD risk factor, comorbidities, index hospitalization, characteristics health plan,	12 years	CVD
Angriman 2023^[48]	Retrospective cohort	268,259	72.0	57.7	Population non-sepsis control group	Age, sex, and race, multiple comorbidities	5 years	CVD, MI, stroke
Angriman 2023^[49]	Matched cohort	157,276	71.3 (14.2)	54.8	Population non-sepsis control group	Age, sex, pre-existing, DM	5 years	CVD, MI, stroke

Table 1.

Figure 1.

Table 2.

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Outcomes	n (studies)	n (participants)	HR (95% CI)	I²
Major cardiovascular events	8	3,776,262	1.54 (1.32, 1.79)	99.6%
Myocardial infarction	8	1,616,592	1.41 (1.29, 1.54)	89.9%
Stroke	11	1,842,169	1.45 (1.32, 1.60)	94.8%
Congestive heart failure	4	2,979,028	1.51 (1.46, 1.56)	74.4%

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