The combined effects of depression or anxiety with high-sensitivity C-reactive protein in predicting the prognosis of coronary heart disease patients

Abstract

Background

Depression, anxiety and high-sensitivity C-reactive protein (hs-CRP) are individually associated with poor prognosis in patients with coronary heart disease (CHD). However, the combined effects of depression with inflammation or anxiety with inflammation on the prognosis have been rarely explored.

Methods

This prospective cohort study included 414 patients diagnosed with CHD. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess depression and anxiety. A score ≥ 5 points was defined as elevated depression or anxiety. High hs-CRP was defined as ≥ 3 mg/L. Follow-up was performed 2 years after the patients were discharged. The clinical results included noncardiac readmission, cardiac readmission, major cardiovascular events (MACEs), and composite events. The composite events included noncardiac readmission and MACEs. The Cox proportional hazard regression model was used to analyze the prognostic risk.

Results

After full adjustment, patients with elevated depression and high hs-CRP had a higher risk in predicting noncardiac readmission (hazard ratio (HR) = 3.87, 95% confidence interval (CI) = 1.10–9.02, p = 0.002) and composite events (HR = 1.93, 95% CI = 1.13–3.30, p = 0.016) than those with high hs-CRP alone. For the anxiety and hs-CRP group, high hs-CRP alone predicted a higher risk of noncardiac readmission (HR = 3.32, 95% CI = 1.57–7.03, p = 0.002) and composite events (HR = 1.75, 95% CI = 1.12–2.76, p = 0.015) than references. Elevated anxiety had no significant effects on all the endpoints. Furthermore, we didn’t find interactions between depression and hs-CRP or anxiety and hs-CRP.

Conclusion

In patients with CHD, elevated depression with high hs-CRP was found to be significant in predicting the risk of noncardiac readmission and composite events. Early diagnosis and treatment of depression with inflammation are necessary in CHD patients.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12888-024-06158-4.

Introduction

Depression and anxiety are significantly associated with poor prognosis among patients with CHD [1–4]. Although traditional risk factors for CHD and its prognosis are relatively well-understood, the effects of psychosocial factors, especially depression and anxiety, remain under investigation. Studies have shown that depression increases the risk of death and nonfatal cardiac events by 2 to 3 times in patients with CHD. Anxiety may also predict recurrent cardiovascular events in patients diagnosed with myocardial infarction or unstable angina pectoris [5–7].

Inflammation plays a role in all stages of atherosclerosis, from plaque formation to cardiovascular disease (CVD) events [8]. CRP is considered to be a reliable indicator for predicting future cardiovascular events, such as myocardial infarction and stroke [9–11]. CPR is also an important auxiliary factor in the pathophysiological mechanism of mental disorders [12, 13], particularly when combined with depression or anxiety. A recent meta-analysis showed that depression and anxiety are associated with high levels of inflammatory markers, such as C-reactive protein [14–19]. However, there is little research demonstrating the comorbidity of depression with inflammation or anxiety with inflammation on clinical prognosis in patients with CHD.

We conducted an observational study to explore the effects of depression and hs-CRP or anxiety and hs-CRP on the clinical prognoses of CHD patients.

Methods

Subject and design

A total of 705 patients who were initially diagnosed with CHD at hospital admission were investigated from October 2017 to January 2018 in Guangdong Provincial People’s Hospital. The clinical data, including information from clinical examinations, coronary angiographies, and discharge diagnoses, were obtained from the clinical case system. We used the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 Questionnaire (GAD-7) to assess depression and anxiety. All patients filled out the scales independently when their condition was relatively stable, and a well-trained psycho-cardiologist explained the scale to the patients one day before the operation. A total of 705 copies of both PHQ-9 and GAD-7 were retrieved. This study was approved by the Ethics Committee of Guangdong Provincial People’s Hospital. Written informed consent was obtained from all participants.

Based on the results of coronary angiography and discharge diagnoses, 443 patients diagnosed with angina pectoris, according to the Braunwald criteria (187 stable angina pectoris and 256 unstable angina pectoris), were recruited.

Inclusion criteria

1. The patient’s major discharge diagnosis was angina pectoris.

2. The patient had a history of coronary artery bypass grafting and/or intracoronary stent implantation or at least one epicardial coronary artery stenosis (≥ 50%) by coronary angiography.

3. The patient agreed to participate in this study and completed the PHQ-9 and GAD-7 questionnaires.

Exclusion criteria

(1) Participants with myocardial infarction severe valvular heart disease or severe cardiomyopathy that were not due to coronary artery stenosis and those with severe complications.

(2) Patients with cognitive impairment who were unable to complete the survey.

(3) Patients who had completed the percutaneous coronary intervention at the time of assessment.

Depression and anxiety measurement

PHQ-9 and GAD-7 scales are open-source tools and used to evaluate depression and anxiety, respectively [20, 21].

Evaluation of depression

PHQ-9 was utilized to assess each patient’s level of depression in the past 2 weeks. The scale consists of nine items, each scored on a four-point scale (0–3 points). The final score is the sum of the scores from each item. A total score of 0–4 points indicates no depression, 5–9 points indicates mild depression, 10–14 points indicates moderate depression, 15–19 points indicates moderate to severe depression, and 20–27 points indicates severe depression. Patients with PHQ-9 scores of ≥ 5 were considered to have depression.

Evaluation of anxiety

The GAD-7 scale was used to assess the anxiety level of the patients in the past 2 weeks. The scale includes seven items, each scored on a four-point scale (0–3 points). The final score is the sum of the scores from each item. A total score of 0–4 points indicates no anxiety, 5–9 points indicates mild anxiety, 10–14 points indicates severe anxiety, and 15–21 points indicates severe anxiety. A score of ≥ 5 is widely used as the threshold for anxiety [22]. These two scales have achieved high reliability and validity among Chinese cardiac patients [23, 24].

High-sensitivity C-Reactive protein and other variables

Hs-CRP was assessed from blood drawn by professional nurses and measured using latex particle intensified immunity transmission turbidity in the laboratory of Guangdong Provincial People’s Hospital. Twenty-nine patients with over 20 mg/L of hs-CRP were removed from the analysis because of the possibility of acute infection. A cut-off value of 3 mg/L was used to differentiate between patients with normal and abnormal levels of hs-CRP. After excluding patients with hs-CRP levels over 20 mg/L, a total of 414 patients were included in the final analysis (Fig. 1).

Fig. 1.

Study flowchart

Other variables

Baseline data included gender, age, body mass index, and marital status. Coronary artery stenosis was classified into 1st, 2nd, and 3rd grades according to the number of coronary arteries with stenosis ≥ 50%. Stenosis involving the left main coronary artery with ≥ 30% stenosis was classified as 3rd -grade coronary artery stenosis. High blood pressure, diabetes mellitus, hyperlipidemia, level of lipoprotein(a) (Lpa), and medication use were obtained from electronic medical records. Patients were defined as having comorbidity if they had either high blood pressure, diabetes mellitus or hyperlipidemia.

Patients classifications

We divided patients into different subgroups by combining the depression and hs-CRP or anxiety and hs-CRP into a categorical variable comprising low depression with low hs-CRP or low anxiety with low hs-CRP (reference group), low depression with high hs-CRP or low anxiety with high hs-CRP, elevated depression with low hs-CRP or anxiety with low hs-CRP, and elevated depression with high hs-CRP or anxiety symptoms with high hs-CRP.

Endpoints

Follow-up assessments were performed by telephone at 2 years after discharge. The follow-up endpoint event was cardiac and noncardiac readmission, MACEs and composite events. Noncardiac readmission refers to noncardiac diseases which need to be readmitted for further treatment. MACEs consisted of death, nonfatal stroke, cardiac readmission, revascularisation, and recurrence of nonfatal myocardial infarction. The composite event incorporated both noncardiac readmissions and MACEs.

Statistical analysis

Baseline characteristics were displayed as mean ± standard deviation, median (interquartile range), or number (percentage). Kaplan–Meier survival curves and the Log-Rank test were used for survival analysis between depression and hs-CRP or anxiety and hs-CRP. The Cox proportional hazard regression model was used to analyze the effects of all groups on readmission, MACE, and composite endpoint events and calculate the hazard ratio (HR) value and 95% CI. Variables with P < 0.1 in univariate analysis or those with clinical significance were adjusted in the multivariate analysis. Two models were developed for adjustment: Model 1 included gender, age and marital status; Model 2 added comorbidity, level of lipoprotein (a), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and calcium channel blocker to model 1. The variable of Lp(a) had a missing rate of 3.1% (13/414), and missing values were imputed using the series mean. All analyses were conducted using SPSS version 22. Two-tailed tests were used in the analysis, and a P value of < 0.05 indicated that the difference was statistically significant.

Results

Baseline characteristic

A total of 414 patients were enrolled in this study, all of whom completed PHQ-9 and GAD-7 questionnaires. The baseline characteristics of the participants are shown in Table 1. The average age was 63.7 ± 9.7 years old. Three-quarters of the patients were male. Around 60% of patients suffered from three coronary artery stenosis. Besides, 62.3% of patients had high blood pressure, 33.6% had diabetes and 65.9% had hyperlipidemia. Medication usage was also recorded. Based on the cut-off value of 5 points, 37.7% of patients exhibited elevated depression and 28.7% of patients had elevated anxiety. In addition, patients were divided into two subgroups: one for depression and hs-CRP and the other for anxiety and hs-CRP. The specific population distribution is detailed in Table 1.

Table 1.

Baseline characteristics of the study population

Characteristics	N = 414
Age, mean ± SD, y	63.7 ± 9.7
Gender, n(%)
Male	315(76.1)
Female	99(23.9)
Marriage, n(%)
Divorced/Widowed/Single	29(7.0)
Married	385(93.0)
BMI, mean ± SD, kg/m2	24.9 ± 3.0
Severity of coronary artery stenosis, n(%)
1	88(21.3)
2	78(18.8)
3	248(59.9)
Comorbidity
High blood pressure, n(%)	258(62.3)
Diabetes mellitus, n(%)	139(33.6)
Hyperlipidemia	273(65.9)
Lipoprotein (a), mmol/L	145(278.5)
Medications
ACEI/ARB	295(71.3)
Beta blocker	361(87.2)
CCB	106(25.6)
PHQ-9	3(5)
Elevated depression, n(%)	156(37.7)
GAD-7	2(4)
Elevated anxiety, n(%)	119(28.7)
Hs-CRP	1.9(2.4)
Hs-CRP ≥ 3 mg/L, n(%)	109(26.3)
Subgroup, n(%)
Depression and hs-CRP
(－)depression (－) hs-CRP	201(48.6)
(＋)depression (－) hs-CRP	104(25.1)
(－) depression (＋) hs-CRP	57(13.8)
(＋) depression (＋) hs-CRP	52(12.6)
Anxiety and hs-CRP
(－)anxiety (－) hs-CRP	216(52.2)
(＋)anxiety (－) hs-CRP	89(21.5)
(－) anxiety (＋) hs-CRP	79(19.1)
(＋)anxiety (＋) hs-CRP	30(7.2)

Variables are shown as mean ± standard deviation, median (Interquartile range), or number (Percentage)

ACRI/ARB: angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; CCB: calcium channel blocker; PHQ-9: Patient Health Questionnaire-9; GAD-7: Generalized Anxiety Disorder-7; Hs-CRP: high-sensitivity C-reactive protein

Follow-Up events

During the follow-up period of 25 months to 29 months, 72 patients had cardiac readmissions, 40 patients had noncardiac readmissions, 84 patients had MACEs, and 119 patients had composite events. In univariate analysis, for the noncardiac readmission, patients with elevated depression and high hs-CRP had a higher incidence than the reference (HR = 4.29, 95% CI = 1.86–9.89, p = 0.001) (Fig. 2A) (Table 2). For the composite endpoint, high hs-CRP (HR = 1.70, 95% CI = 1.00–2.86, p = 0.048) alone and elevated depression with high hs-CRP (HR = 1.77, 95% CI = 1.05–2.99, p = 0.033) predicted greater risk than the reference (Fig. 2B). No statistical significances were observed in the cardiac readmission and MACE for the depression and hs-CRP groups. For the anxiety and hs-CRP group, hs-CRP alone was a predictor of noncardiac readmission (HR = 3.00, 95% CI = 1.43–6.30, p = 0.004) and composite event (HR = 1.64, 95% CI = 1.05–2.58, p = 0.031) (Fig. 2C, D) (Table 3).

Fig. 2.

Kaplan–Meier curves of study endpoints. A: Kaplan Meier curves of 2-year noncardiac readmission in CHD patients with different level of depression and hs-CRP; B: Kaplan Meier curves of 2-year composite events in CHD patients with different level of depression and hs-CRP; C: Kaplan Meier curves of 2-year noncardiac readmission in CHD patients with different level of anxiety and hs-CRP; D: Kaplan Meier curves of 2-year composite events in CHD patients with different level of anxiety and hs-CRP

Table 2.

Results for depression and hs-CRP as predictors of follow-up events

Endpoints	Group	Number of event(%)	Univariate		Model 1		Model 2
			HR(95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Cardiac Readmission N = 72	(－)depression/(－)hs-CRP	31(43.1)	Reference
	(＋)depression/(－)hs-CRP	20(27.8)	1.30(0.74–2.29)	0.356	1.42(0.80–2.52)	0.226	1.44(0.81–2.56)	0.213
	(－)depression/(＋)hs-CRP	13(18.1)	1.55(0.81–2.96)	0.185	1.58(0.83–3.04)	0.167	1.61(0.84–3.08)	0.154
	(＋)depression/(＋)hs-CRP	8(11.1)	1.00(0.46–2.18)	> 0.99	1.16(0.53–2.51)	0.722	1.23(0.56–2.70)	0.604
Noncardiac readmission N = 40	(－)depression/(－)hs-CRP	11(27.5)	Reference
	(＋)depression/(－)hs-CRP	11(27.5)	2.03(0.88–4.68)	0.098	1.81(0.77–4.24)	0.172	2.00(0.84–4.74)	0.117
	(－)depression/(＋)hs-CRP	7(17.5)	2.33(0.90-6.00)	0.080	2.16(0.83–5.60)	0.113	2.48(1.00-6.83)	0.049*
	(＋)depression/(＋)hs-CRP	11(27.5)	4.29(1.86–9.89)	0.001*	3.47(1.47–8.19)	0.004*	3.87(1.61–9.02)	0.002*
MACEs N = 84	(－)depression/(－)hs-CRP	35(41.7)	Reference
	(＋)depression/(－)hs-CRP	24(28.6)	1.41(0.84–2.38)	0.191	1.50(0.86–2.48)	0.162	1.51(0.89–2.56)	0.131
	(－)depression/(＋)hs-CRP	13(15.5)	1.40(0.74–2.64)	0.305	1.41(0.74–2.68)	0.291	1.44(0.76–2.74)	0.262
	(＋)depression/(＋)hs-CRP	12(14.3)	1.35(0.70–2.60)	0.369	1.50(0.77–2.90)	0.232	1.59(0.82–3.09)	0.173
Composite N = 119	(－)depression/(－)hs-CRP	47(39.5)	Reference
	(＋)depression/(－)hs-CRP	32(26.9)	1.42(0.91–2.23)	0.126	1.41(0.90–2.22)	0.144	1.49(0.94–2.37)	0.088
	(－)depression/(＋)hs-CRP	20(16.8)	1.70(1.00-2.86)	0.048*	1.67(0.99–2.83)	0.057	1.79(1.06–3.03)	0.031*
	(＋)depression/(＋)hs-CRP	20(16.8)	1.77(1.05–2.99)	0.033*	1.81(1.06–3.07)	0.029*	1.93(1.13–3.30)	0.016*

(－)depression means no elevated depression; hs-CRP ≤ 3 mg/L; (＋)depression means elevated depression; hs-CRP means 3mg/L< hs-CRP<20 mg/L

Model 1: Gender, age, marriage

Model 2: Model 1, comorbidity of high blood pressure, diabetes mellitus and hyperlipidemia, lipoprotein(a), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and calcium channel blocker

*: P < 0.05

Table 3.

Results for anxiety and hs-CRP as predictors of follow-up events

Endpoints	Group	Number of event(%)	Univariate		Model 1		Model 2
			HR(95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Cardiac Readmission N = 72	(－)anxiety/(－)hs-CRP	38(52.8)	Reference
	(＋)anxiety/(－)hs-CRP	13(18.1)	0.85(0.45–1.60)	0.613	0.84(0.44–1.60)	0.596	0.87(0.45–1.65)	0.660
	(－)anxiety/(＋)hs-CRP	15(20.8)	1.13(0.62–2.05)	0.699	1.18(0.65–2.14)	0.597	1.18(0.65–2.15)	0.593
	(＋)anxiety/(＋)hs-CRP	6(8.3)	1.09(0.46–2.58)	0.846	1.15(0.48–2.73)	0.752	1.32(0.55–3.17)	0.530
Noncardiac readmission N = 40	(－)anxiety/(－)hs-CRP	14(35.0)	Reference
	(＋)anxiety/(－)hs-CRP	8(20.0)	1.43(0.60–3.41)	0.419	1.44(0.59–3.52)	0.428	1.42(0.57–3.54)	0.447
	(－)anxiety/(＋)hs-CRP	14(35.0)	3.00(1.43–6.30)	0.004*	2.76(1.31–5.81)	0.007*	3.32(1.57–7.03)	0.002*
	(＋)anxiety/(＋)hs-CRP	4(10.0)	2.02(0.67–6.14)	0.215	1.69(0.55–5.19)	0.357	1.62(0.52–5.08)	0.409
MACEs N = 84	(－)anxiety/(－)hs-CRP	41(48.8)	Reference
	(＋)anxiety/(－)hs-CRP	18(21.4)	1.10(0.63–1.92)	0.727	1.05(0.59–1.84)	0.879	1.08(0.61–1.91)	0.797
	(－)anxiety/(＋)hs-CRP	17(20.2)	1.20(0.68–2.11)	0.527	1.25(0.70–2.19)	0.459	1.26(0.71–2.22)	0.428
	(＋)anxiety/(＋)hs-CRP	8(9.5)	1.35(0.63–2.89)	0.435	1.38(0.64–2.95)	0.413	1.50(0.69–3.26)	0.301
Composite N = 119	(－)anxiety/(－)hs-CRP	55(46.2)	Reference
	(＋)anxiety/(－)hs-CRP	24(20.2)	1.09(0.67–1.76)	0.734	1.06(0.65–1.73)	0.822	1.10(0.67–1.81)	0.695
	(－)anxiety/(＋)hs-CRP	29(24.4)	1.64(1.05–2.58)	0.031*	1.64(1.05–2.59)	0.031*	1.75(1.12–2.76)	0.015*
	(＋)anxiety/(＋)hs-CRP	11(9.2)	1.38(0.72–2.64)	0.328	1.36(0.71–2.60)	0.359	1.43(0.74–2.77)	0.291

(－)anxiety means no elevated anxiety; hs-CRP ≤ 3 mg/L

(＋)anxiety means elevated anxiety; hs-CRP means 3mg/L< hs-CRP<20 mg/L

Model 1: Gender, age, marriage

Model 2: Model 1, comorbidity of high blood pressure, diabetes mellitus and hyperlipidemia, lipoprotein(a), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and calcium channel blocker

*: P < 0.05

After fully adjusted, for the noncardiac readmission, patients with high hs-CRP alone (HR = 2.48, 95% CI = 1.00–6.83, p = 0.049) and with both elevated depression and high hs-CRP (HR = 3.87, 95% CI = 1.61–9.02, p = 0.002) (Table 2) predicted a greater risk than the reference. The incidence of composite events was also significantly increased in patients with high hs-CRP alone (HR = 1.79, 95% CI = 1.06–3.03, p = 0.031) and in those with elevated depression and high hs-CRP (HR = 1.93, 95% CI = 1.13–3.30, p = 0.016). Elevated depression with low hs-CRP showed a tendency to predict noncardiac readmission, MACEs and composite events. For the anxiety and hs-CRP group, after fully adjusted in model 2, high hs-CRP alone predicted a higher risk of noncardiac readmission (HR = 3.32, 95% CI = 1.57–7.03, p = 0.002) and composite events (HR = 1.75, 95% CI = 1.12–2.76, p = 0.015) with greater HRs than those in univariate analysis (Table 3). Elevated anxiety alone had no significant effects on all the endpoints.

Additionally, we analyzed depression and hs-CRP as binary variables in one model, anxiety and hs-CRP as well. The independent effects of depression or anxiety or hs-CRP on prognoses have been shown in Additional Table 1. And we didn’t find interactions between depression and hs-CRP or anxiety and hs-CRP (Additional Table 1).

Discussion

This study revealed the effects of depression with hs-CRP or anxiety with hs-CRP on the different prognoses in patients with CHD. Our findings indicated that patients with depression and high hs-CRP levels had a higher risk of noncardiac readmission and composite events than the reference group. Elevated hs-CRP alone was also identified as a risk factor for noncardiac readmission and composite events. However, anxiety did not show a significant effect on prognosis.

The most thought-provoking finding of this study was the poor prognosis of depression with high hs-CRP for noncardiac readmission and composite events among patients with CHD. Previous studies have shown that patients with both CHD and depression exhibited a high mortality rate and occurrence of readmission, which aggravates the severity of the disease, increases medical costs and leads to the wastage of resources [25, 26]. Inflammation is central to the pathogenesis of atherosclerosis. The most extensively studied biomarker of inflammation related to the risk of CHD is hs-CRP [9] which is associated with various diseases, such as diabetes, weight gain, and hypertension [27, 28]. A study on patients with acute heart failure showed that significantly rising CRP levels at admission may lead to high rates of noncardiac mortality [29]. Poople et al. [30] illustrated that depression and elevated CRP were risk factors for CHD, stroke, diabetes, hyperglycemia, and lung disease, which can increase the further readmission rates. Compared to the reference group, depression showed a tendency to predict noncardiac readmission, MACE and composite events. Depression has been indicated as a risk factor for poor medical outcomes in patients with CHD [4, 31, 32]. Depression can lead to various somatic symptoms, and its coexistence with inflammation may increase the incidence of noncardiac diseases. Given that we didn’t observe the interaction between depression and hs-CRP, these effects appeared to be independent, and the comorbidity of elevated depression and high hs-CRP pose greater risks in predicting noncardiac readmission and composite events than one exposure alone.

In the analysis with anxiety and hs-CRP, we found that high hs-CRP, rather than anxiety symptoms, increased the risk of noncardiac readmission and composite events. This finding aligns with results from several inflammation-associated studies. The literature shows that chronic inflammation increases a range of adverse health outcomes, such as congestive heart failure [33], type 2 diabetes [34], inflammatory bowel disease [35], chronic obstructive pulmonary disease [36], cancer [37]. We did not identify any effects of anxiety on prognoses. The definition of elevated anxiety was a GAD-7 score of ≥ 5, representing mild anxiety. General acute anxiety symptoms are transient and triggered by a patient’s temporary perception of stress or threat, once this stress or threat is reduced, the anxiety symptoms will be reduced accordingly.

However, we didn’t find significant effects of depression, anxiety, or high hs-CRP on cardiac readmission or MACEs. In this research, the definition of elevated depression was a PHQ-9 score of ≥ 5, indicating mild depression. It is possible that clinical depression (PHQ-9 score of ≥ 10) may have a greater impact on cardiac events than mild depression [38]. The effects of anxiety on cardiac events remained controversial [39]. Some studies suggested that anxiety may independently predict cardiac events after acute myocardial infarction [40–42], while other studies indicated that anxiety may reduce the occurrence of cardiac events in patients with stable CHD [43, 44]. Furthermore, in our study, hs-CRP was not identified as the predictor of cardiac readmission and MACEs. There might be several reasons for this. Firstly, the population primarily consists of angina pectoris patients, excluding severe conditions like myocardial infarction or heart failure [29]. Secondly, the follow-up period is 2 years, whereas other related studies often have longer follow-up periods, such as 5 to 10 years [11]. Additionally, there might be differences within subgroups (such as gender or age). Moreover, the cut-off value of hs-CRP could also be a contributing factor, and some studies used a cut-off of 2 mg/L or 5 mg/L [45].

The major strengths of our study include our initial exploration of the effects of depression with high hs-CRP on noncardiac prognosis and composite events. And whether anxiety existed or not, it didn’t affect the impact of hs-CRP on the prognosis of patients with CHD. However, this study has several limitations. We only collected hs-CRP measurements and psychiatric assessments once at baseline, and it would be better to measure it multiple times to observe changes. Although we did not conduct professional psychiatric interviews to confirm the diagnosis of psychiatric symptoms, we used anxiety and depression screening tools that are easy to implement and have been fully validated. Furthermore, our study was limited to a single hospital, which ensured consistency in examination tools, methods, follow-up times, and procedures but limited the universality and generalizability of our findings.

Conclusions

To sum up, among patients with CHD, the comorbidity of elevated depression and high hs-CRP levels have greater risks in predicting noncardiac readmission and composite events than one exposure alone, but no effect of anxiety on this prognosis was identified. More attention should be paid to patients with depression and inflammation clinically. This reflects the complexity of the roles of depression, anxiety, and inflammation in various prognostic outcomes. It highlights the necessity for future research to explore the correlation mechanisms between mood symptoms, pathophysiological changes, and somatic diseases in patients with CHD.

Electronic supplementary material

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Abbreviations

Hs-CRP

high-sensitivity C-reactive protein

CHD

coronary heart disease

PHQ-9

patient health questionnaire-9

GAD-7

generalized anxiety disorder-7

MACEs

major cardiovascular events

HR

hazard ratio

CI

confidence interval

CVD

cardiovascular disease

Lpa

lipoprotein(a)

Author contributions

BB and HY surveyed the prognostic information. HY, HW, FL, YL, and AL collected the baseline data and entered data into the database. BB and HY did the statistical analyses. BB and HY wrote the first draft. QG, LG, and HM revised the paper. QG, LG and HM were senior physicians principally responsible for the study. All authors read and approved the final manuscript.

Funding

This research was supported by the grants from High level Hospital Construction Project of Guangdong Provincial People’s Hospital (DFJH2020029), and Guangzhou Municipal Science and Technology Program key projects (2023B03J1249).

Data availability

The datasets obtained and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Ethical approval was given by the medical ethics committee of Guangdong Provincial People’s Hospital with the following reference number: No. GDREC2017203H. All participants gave written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.