Inflammation modifies the platelet reactivity among thrombocytopenia patients undergoing percutaneous coronary intervention

Figures & data

Inflammation modifies platelet reactivity of PCI patients with thrombocytopenia.

CI, confidence interval; hsCRP, high-sensitivity C-reactive protein; HTPR, high on-treatment platelet reactivity; OR, odds ratio; PCI, percutaneous coronary intervention; TP, thrombocytopenia.

Figure 1. Flowchart of patients enrolled in the study cohort.

hsCRP, high-sensitivity C-reactive protein; PCI, percutaneous coronary intervention.

Table I. Baseline characteristics of patients according to platelet reactivity.

Variables	Non-HTPR (n = 4592)	HTPR (n = 2025)	p value
Thrombocytopenia	688 (15.0)	191 (9.4)	<.001***
Platelet count, 10^9/L	200.21 ± 52.61	216.69 ± 58.54	<.001^***
hsCRP, mg/L	1.43 (0.73, 3.04)	2.16 (1.06, 5.37)	<.001^***
Age, year	57.50 ± 10.26	59.95 ± 10.14	.040^***
Male	3858 (84.0)	1274 (62.9)	<.001^***
BMI, kg/m^2	25.97 ± 3.17	25.97 ± 3.17	.979
Smoking history	2855 (62.2)	993 (49.0)	<.001^***
ACS	2571 (56.0)	1219 (60.2)	.001^***
COPD	102 (2.2)	48 (2.4)	.707
PAD	123 (2.7)	66 (3.3)	.191
Diabetes	1327 (28.9)	689 (34.0)	<.001^***
Hypertension	2949 (64.2)	1355 (66.9)	.034^***
Hyperlipidemia	3134 (68.2)	1371 (67.7)	.661
Prior stroke	455 (9.9)	227 (11.2)	.109
Prior MI	957 (20.8)	344 (17.0)	<.001^***
Prior PCI	1179 (25.7)	445 (22.0)	.001^***
Prior CABG	198 (4.3)	74 (3.7)	.214
LVEF, %	62.98 ± 7.19	62.78 ± 7.37	.308
Hemoglobin, g/L	145.38 ± 14.54	136.82 ± 14.99	<.001^***
MPV, fL	10.61 ± 0.92	10.59 ± 0.90	.408
Triglyceride, mmol/L	1.77 ± 1.08	1.81 ± 1.01	.194
LDL-C, mmol/L	2.44 ± 0.90	2.60 ± 0.91	<.001^***
HDL-C, mmol/L	1.02 ± 0.27	1.04 ± 0.28	.106
Glucose, mmol/L	6.02 ± 1.87	6.28 ± 2.14	<.001^***
eGFR, ml/min	92.51 ± 14.36	89.87 ± 15.40	<.001^***

Values were mean ± standard deviation, median (interquartile range) or n (%).

ACS, acute coronary syndrome; BMI, body mass index; CABG, coronary artery bypass grafting; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein-cholesterol; hsCRP, high-sensitivity C-reactive protein; HTPR, high on-treatment reactivity; LDL-C, low-density lipoprotein-cholesterol; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MPV, mean platelet volume; PAD, peripheral artery disease; PCI, percutaneous coronary intervention.

***p values indicating statistical significance.

Table II. Univariate and multivariate logistic regression for HTPR in entire cohort.

	Univariate logistic regression			Multivariate logistic regression
	Crude OR	95% CI	p value	Adjusted OR	95% CI	p value
Thrombocytopenia	0.59	0.50–0.70	<.001***	0.64	0.53–0.76	<.001^***
hsCRP	1.09	1.08–1.11	<.001^***	1.08	1.06–1.10	<.001^***
Male	0.32	0.29–0.36	<.001^***	0.58	0.49–0.69	<.001^***
Age	1.02	1.02–1.03	<.001^***	1.00	1.00–1.01	.256
BMI	1.00	0.98–1.02	.979	-	-	-
Smoking history	0.59	0.53–0.65	<.001^***	0.96	0.84–1.10	.542
ACS	1.19	1.07–1.32	.001^***	1.04	0.93–1.17	.492
COPD	1.07	0.76–1.51	.707	-	-	-
PAD	1.22	0.90–1.66	.192	-	-	-
Diabetes	1.27	1.14–1.42	<.001^***	1.15	1.00–1.33	.057
Hypertension	1.13	1.01–1.26	.034^***	0.94	0.83–1.06	.302
Hyperlipidemia	0.98	0.87–1.09	.661	-	-	-
Prior stroke	1.15	0.97–1.36	.109	-	-	-
Prior MI	0.78	0.68–0.89	<.001^***	0.99	0.84–1.15	.848
Prior PCI	0.82	0.72–0.92	.001^***	0.89	0.78–1.02	.104
Prior CABG	0.84	0.64–1.11	.215	-	-	-
LVEF	1.00	0.99–1.00	.308	-	-	-
Hemoglobin	0.96	0.96–0.97	<.001^***	0.97	0.97–0.97	<.001^***
MPV	0.98	0.92–1.03	.408	-	-	-
Triglyceride	1.03	0.98–1.08	.195	-	-	-
LDL-C	1.21	1.14–1.28	<.001^***	1.20	1.13–1.28	<.001^***
HDL-C	1.17	0.97–1.42	.106	-	-	-
Glucose	1.07	1.04–1.09	<.001^***	1.04	1.01–1.08	.015^***
eGFR	0.99	0.99–0.99	<.001^***	1.00	0.99–1.00	.737

Multivariate logistic regression model was adjusted for variables significant in the univariate model.

ACS, acute coronary syndrome; BMI, body mass index; CABG, coronary artery bypass grafting; CI, confidence interval; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein-cholesterol; hsCRP, high-sensitivity C-reactive protein; HTPR, high on-treatment platelet reactivity; LDL-C, low-density lipoprotein-cholesterol; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MPV, mean platelet volume; OR, odds ratio; PAD, peripheral artery disease; PCI, percutaneous coronary intervention.

***p values indicating statistical significance.

Figure 2. Multivariate logistic regression for HTPR stratified by hsCRP.

ORs and 95% CIs are shown for HTPR. p value represents interaction test between the hsCRP and thrombocytopenia. Multivariate logistic regression models in each group were adjusted for significant variables of univariate logistic regression, as shown in Table III.

CI, confidence interval; hsCRP, high-sensitivity C-reactive protein; HTPR, high on-treatment platelet reactivity; OR, odds ratio.

Table III. Univariate logistic regression for HTPR stratified by hsCRP levels.

	hsCRP <2 mg/L group			hsCRP ≥2 mg/L group
	Crude OR	95% CI	p value	Crude OR	95% CI	p value
Thrombocytopenia	0.49	0.39–0.63	<.001***	0.82	0.63–1.05	.111
Male	0.27	0.23–0.32	<.001^***	0.40	0.33–0.47	<.001^***
Age	1.02	1.02–1.03	<.001^***	1.02	1.02–1.03	<.001^***
BMI	0.98	0.96–1.07	.141	1.00	0.98–1.02	.917
Smoking history	0.53	0.46–0.62	<.001^***	0.59	0.51–0.69	<.001^***
ACS	1.01	0.87–1.17	.897	1.21	1.03–1.42	.020^***
COPD	1.17	0.68–1.99	.576	0.88	0.56–1.40	.592
PAD	1.25	0.82–1.91	.310	1.19	0.76–1.85	.451
Diabetes	1.17	1.00–1.38	.047^***	1.33	1.14–1.57	<.001^***
Hypertension	1.17	1.01–1.37	.042^***	0.99	0.84–1.17	.938
Hyperlipidemia	0.93	0.79–1.08	.328	1.04	0.88–1.22	.643
Prior stroke	1.06	0.83–1.36	.621	1.18	0.93–1.50	.174
Prior MI	0.76	0.63–0.91	.004^***	0.86	0.71–1.06	.161
Prior PCI	0.73	0.61–0.87	<.001^***	1.01	0.84–1.21	.955
Prior CABG	0.72	0.48–1.08	.111	0.98	0.67–1.44	.914
LVEF	1.01	0.99–1.02	.254	0.99	0.98–1.00	.211
Hemoglobin	0.96	0.95–0.96	<.001^***	0.97	0.96–0.97	<.001^***
MPV	0.96	0.89–1.04	.312	1.01	0.92–1.09	.915
Triglyceride	1.02	0.95–1.10	.527	1.00	0.93–1.07	.879
LDL-C	1.27	1.17–1.38	<.001^***	1.07	0.98–1.16	.123
HDL-C	1.68	1.31–2.17	<.001^***	1.07	0.79–1.44	.668
Glucose	1.06	1.02–1.10	.003^***	1.04	1.01–1.08	.021^***
eGFR	0.99	0.98–0.99	<.001^***	0.99	0.98–0.99	<.001^***

ACS, acute coronary syndrome; BMI, body mass index; CABG, coronary artery bypass grafting; CI, confidence interval; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein-cholesterol; HTPR, high on-treatment platelet reactivity; LDL-C, low-density lipoprotein-cholesterol; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MPV, mean platelet volume; OR, odds ratio; PAD, peripheral artery disease; PCI, percutaneous coronary intervention.

***p values indicating statistical significance.

Table IV. Combined effect of hsCRP and TP for HTPR.

		Univariate logistic regression		Multivariate logistic regression
Risk groups	HTPR/Total (%)	OR (95% CI)	p value	OR (95% CI)	p value
hsCRP ≥2 mg/L without TP	967/2498 (38.7%)	Reference	NA	Reference	NA
hsCRP ≥2 mg/L with TP	103/303 (34.0%)	0.82 (0.63–1.05)	.111	0.86 (0.66–1.12)	.272
hsCRP <2 mg/L without TP	867/3240 (26.8%)	0.58 (0.52–0.65)	<.001^***	0.64 (0.57–0.73)	<.001^***
hsCRP <2 mg/L with TP	88/576 (15.3%)	0.29 (0.22–0.36)	<.001^***	0.33 (0.26–0.43)	<.001^***

The multivariate logistic regression model was adjusted for age, sex, smoking history, acute coronary syndrome, diabetes, hypertension, prior myocardial infarction, prior percutaneous coronary intervention, hemoglobin, low-density lipoprotein cholesterol, glucose, and estimated glomerular filtration rate, all of which were significant variables in the univariate model for HTPR in the entire cohort, as shown in Table II.

CI, confidence interval; hsCRP, high-sensitivity C-reactive protein; HTPR, high on-treatment platelet reactivity; NA, not applicable; OR, odds ratio; TP, thrombocytopenia.

***p values indicating statistical significance.

Figure 3. Subgroup analyses of the association between thrombocytopenia and HTPR in different hsCRP levels.

ORs and 95% CIs are shown for HTPR. p value represents interaction test between the hsCRP and thrombocytopenia.

ACS, acute coronary syndrome; CCS, chronic coronary syndrome; CI, confidence interval; hsCRP, high-sensitivity C-reactive protein; HTPR, high on-treatment platelet reactivity; OR, odds ratio.

Data availability statement

Due to ethical restrictions related to the consent given by subjects at the time of study commencement, our datasets are available from the corresponding author upon reasonable request after permission of the Institutional Review Board of State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases.