Peripheral Inflammatory Factors and Acute Myocardial Infarction Risk: A Mendelian Randomization Study

TRAITS	YEAR	SOURCES	SAMPLE SIZE	POPULATION/SEX	NO. OF SUITABLE IVS	F STATISTICS
C-reactiveprotein	2018	PMID: 30388399Ligthart et al.	204,402	European/Both	110	41.771
Interleukin-1α	2018	PMID: 29875488Sun et al.	3,301	European/Both	10	10.251
Interleukin-1β	2018	PMID: 29875488Sun et al.	3,301	European/Both	9	10.461
Interleukin-6	2020	PMID: 33067605Folkersen et al.	21,758	European/Both	15	12.016
Interleukin-10	2016	PMID: 27989323Ahola-Olli et al.	7,681	European/Both	12	15.418
Interleukin-18	2020	PMID: 33067605Folkersen et al.	21,758	European/Both	24	20.058
Neutrophilcount	2020	BCCVuckovic et al.	563,946	European/Both	572	31.443
Lymphocytecount	2020	BCCVuckovic et al.	563,946	European/Both	670	32.688
Monocytecout	2020	BCCVuckovic et al.	563,946	European/Both	653	45.533
Acute myocardialinfarction	2022	FinnGenKurki et al.	307,230	European/Both	102	11.499

[i] ^a BCC = Blood Cell Consortium; IV = Instrumental variable.

Effect of inflammatory factors and inflammatory cells on the risk of acute myocardial infarction.^a

EXPOSURES	METHODS	OR (95%CI)	P VALUE^b	P VALUE^c	P VALUE^d
C-reactiveprotein	IVW	0.972 (0.896 ~ 1.055)	0.504	0.027	0.298
	Weighted median	0.947 (0.842 ~ 1.066)	0.367
	MR-Egger	0.920 (0.805 ~ 1.050)	0.220
Interleukin-1α	IVW	1.008 (0.927 ~ 1.095)	0.857	0.301	0.121
	Weighted median	0.978 (0.885 ~ 1.080)	0.660
	MR-Egger	0.353 (0.124 ~ 1.009)	0.124
Interleukin-1β	IVW	0.996 (0.901 ~ 1.101)	0.938	0.092	0.226
	Weighted median	1.009 (0.910 ~ 1.119)	0.867
	MR-Egger	1.359 (0.866 ~ 2.132)	0.239
Interleukin-6	IVW	0.991 (0.888 ~ 1.106)	0.875	0.477	0.234
	Weighted median	0.954 (0.826 ~ 1.102)	0.522
	MR-Egger	1.148 (0.895 ~ 1.473)	0.309
Interleukin-10	IVW	0.876 (0.788 ~ 0.974)	0.015	0.171	0.390
	Weighted median	0.868 (0.767 ~ 0.981)	0.024
	MR-Egger	1.265 (0.572 ~ 2.798)	0.579
Interleukin-18	IVW	0.934 (0.875 ~ 0.997)	0.040	0.603	0.503
	Weighted median	0.916 (0.840 ~ 0.998)	0.045
	MR-Egger	0.898 (0.787 ~ 1.024)	0.125
Neutrophilcount	IVW	1.022 (0.952 ~ 1.097)	0.549	0.063	0.352
	Weighted median	1.053 (0.950 ~ 1.167)	0.325
	MR-Egger	1.099 (0.928 ~ 1.303)	0.273
Lymphocytecount	IVW	1.060 (0.992 ~ 1.131)	0.084	0.072	0.731
	Weighted median	1.029 (0.930 ~ 1.139)	0.580
	MR-Egger	1.084 (0.936 ~ 1.255)	0.280
Monocytecout	IVW	1.047 (0.992 ~ 1.106)	0.095	0.063	0.062
	Weighted median	1.023 (0.929 ~ 1.127)	0.643
	MR-Egger	0.969 (0.879 ~ 1.069)	0.531

[i] ^a IVW = Inverse variance weighted; OR = Odds ratio; CI = Confidence interval.

^b P value for Mendelian randomization.

^c P value for Cochran’s Q test.

^d P value for MR-Egger intercept test.

Effect of acute myocardial infarction on periphery levels of inflammatory factors and inflammatory cells.^a

OUTCOMES	METHODS	OR (95%CI)	P VALUE^b	P VALUE^c	P VALUE^d
C-reactiveprotein	IVW	1.004 (0.982 ~ 1.026)	0.739	0.146	0.097
	Weighted median	0.976 (0.949 ~ 1.004)	0.093
	MR-Egger	0.955 (0.898 ~ 1.015)	0.147
Interleukin-1α	IVW	1.009 (0.927 ~ 1.097)	0.844	0.118	0.782
	Weighted median	0.931 (0.824 ~ 1.051)	0.248
	MR-Egger	1.037 (0.837 ~ 1.285)	0.740
Interleukin-1β	IVW	0.941 (0.870 ~ 1.017)	0.122	0.553	0.665
	Weighted median	0.888 (0.789 ~ 1.001)	0.052
	MR-Egger	0.979 (0.805 ~ 1.191)	0.833
Interleukin-6	IVW	0.992 (0.954 ~ 1.031)	0.671	0.500	0.401
	Weighted median	0.996 (0.934 ~ 1.062)	0.906
	MR-Egger	0.954 (0.865 ~ 1.052)	0.348
Interleukin-10	IVW	1.062 (1.003 ~ 1.124)	0.040	0.404	0.961
	Weighted median	1.008 (0.925 ~ 1.099)	0.848
	MR-Egger	1.058 (0.917 ~ 1.221)	0.440
Interleukin-18	IVW	0.979 (0.943 ~ 1.015)	0.250	0.058	0.148
	Weighted median	0.961 (0.913 ~ 1.012)	0.134
	MR-Egger	0.919 (0.838 ~ 1.008)	0.075
Neutrophilcount	IVW	0.995 (0.987 ~ 1.003)	0.244	0.054	0.252
	Weighted median	0.989 (0.978 ~ 1.002)	0.088
	MR-Egger	0.985 (0.967 ~ 1.004)	0.127
Lymphocytecount	IVW	0.993 (0.985 ~ 1.001)	0.083	0.153	0.455
	Weighted median	0.982 (0.970 ~ 0.994)	0.003
	MR-Egger	0.987 (0.969 ~ 1.005)	0.155
Monocytecout	IVW	1.000 (0.991 ~ 1.009)	0.995	0.149	0.835
	Weighted median	0.994 (0.981 ~ 1.007)	0.356
	MR-Egger	0.998 (0.978 ~ 1.019)	0.853

[i] ^a IVW = Inverse variance weighted; OR = Odds ratio; CI = Confidence interval.

^b P value for Mendelian randomization.

^c P value for Cochran’s Q test.

^d P value for MR-Egger intercept test.

MR-PRESSO results for Mendelian randomization analyses and outlier tests.^a

EXPOSURES	β VALUE	SD	OR (95%CI)	P VALUE FOR MR	P VALUE FOR OUTLIERS
C-reactive protein	–0.028	0.042	0.972 (0.896 ~ 1.056)	0.506	0.032
Interleukin-1α	0.008	0.042	1.008 (0.928 ~ 1.095)	0.864	0.342
Interleukin-1β	–0.004	0.051	0.996 (0.901 ~ 1.101)	0.941	0.124
Interleukin-6	–0.009	0.055	0.991 (0.890 ~ 1.104)	0.875	0.498
Interleukin-10	–0.132	0.054	0.876 (0.788 ~ 0.974)	0.041	0.229
Interleukin-18	–0.068	0.031	0.934 (0.879 ~ 0.993)	0.042	0.665
Neutrophil count	0.022	0.036	1.022 (0.953 ~ 1.097)	0.550	0.064
Lymphocyte count	0.058	0.033	1.060 (0.993 ~ 1.131)	0.084	0.076
Monocyte cout	0.046	0.028	1.047 (0.991 ~ 1.106)	0.096	0.070
OUTCOMES	β VALUE	SD	OR (95%CI)	P VALUE FOR MR	P VALUE FOR OUTLIERS
C-reactive protein	0.004	0.011	1.004 (0.983 ~ 1.026)	0.741	0.145
Interleukin-1α	0.008	0.043	1.008 (0.927 ~ 1.097)	0.844	0.116
Interleukin-1β	–0.061	0.039	0.941 (0.872 ~ 1.016)	0.121	0.567
Interleukin-6	–0.008	0.020	0.992 (0.954 ~ 1.032)	0.671	0.500
Interleukin-10	0.060	0.029	1.062 (1.003 ~ 1.124)	0.044	0.418
Interleukin-18	–0.022	0.019	0.978 (0.942 ~ 1.015)	0.253	0.057
Neutrophil count	–0.005	0.004	0.995 (0.987 ~ 1.003)	0.249	0.053
Lymphocyte count	–0.007	0.004	0.993 (0.985 ~ 1.001)	0.089	0.138
Monocyte cout	2.733e-05	0.004	1.000 (0.992 ~ 1.008)	0.995	0.138